气道平滑肌细胞在哮喘中的作用研究进展
|
摘要
气道平滑肌细胞(ASM)已被证实在支气管哮喘中起重要作用,随着研究深入,其机制愈发复杂,目前具体机制尚不清楚。本文通过对ASM炎症机制、细胞外基质蛋白(EMC)、细胞收缩、细胞结构、神经调节、气道重构、凋亡、自噬、表观遗传学、mirna、线粒体等方面探讨ASM在哮喘中的作用,期望给哮喘临床治疗上提供新的靶点。
Airway smooth muscle cells(ASM) have been shown to play an important role in asthma. as the research progresses, the mechanism of ASM has become more and more complicated. However,the exact mechanism remains unclear. in this review, we investigated the role of ASM in the pathogenesis of asthma in terms of inflammatory mechanisms, extracellular matrix proteins(EMC), contractility, structural aspects, neural control, airway remodeling, apoptosis, autophagy, epigenetic mechanisms, mirnas and mitochondria. expect to provide a new target for the clinical treatment of asthma.
Airway smooth muscle cells(ASM) have been shown to play an important role in asthma. as the research progresses, the mechanism of ASM has become more and more complicated. However,the exact mechanism remains unclear. in this review, we investigated the role of ASM in the pathogenesis of asthma in terms of inflammatory mechanisms, extracellular matrix proteins(EMC), contractility, structural aspects, neural control, airway remodeling, apoptosis, autophagy, epigenetic mechanisms, mirnas and mitochondria. expect to provide a new target for the clinical treatment of asthma.
引文
[1]Koziol-White CJ,Panettieri RA.Jr Airway smooth muscle and immunomodulation in acute exacerbations of airway disease[J].Immunol Rev,2011,242:178-185.
[2]Manetsch M,Seidel P,Heintz u,et al.TLR2 ligand engagement upregulates airway smooth muscle TNFα-induced cytokine production[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L838-L845.
[3]Michaeloudes C,Sukkar MB,Khorasani NM,et al.TGF-βregulates Nox4,Mn So D and catalase expression,and IL-6 release in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L295-L304.
[4]Robinson MB,Deshpande DA,Chou J,et al.IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L129-L138.
[5]Redhu NS,Gounni AS.Function and mechanisms of TSLP/TSLPR complex in asthma and Co PD[J].Clin Exp Allergy,2012,42:994-1005.
[6]Redhu NS,Saleh A,Halayko AJ,et al.Essential role of NF-κB and AP-1transcription factors in TNF-α-induced TSLP expression in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L479-L485.
[7]Baarsma HA,Menzen MH,Halayko AJ,et al.β-Catenin signaling is required for TGF-β1-induced extracellular matrix production by airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,301:L956-L965.
[8]Damera G,Tliba o,Panettieri RA.,Jr Airway smooth muscle as an immunomodulatory cell[J].Pulm Pharmacol Ther,2009,22:353-359.
[9]Alrashdan YA,Alkhouri H,Chen E,et al.Asthmatic airway smooth muscle CXCL10 production:mitogen-activated protein kinase JNK involvement[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L1118-L1127.
[10]Tan X,Alrashdan YA,Alkhouri H,et al.Airway smooth muscle CXCR3ligand production:regulation by JAK-STAT1 and intracellular Ca2+[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L790-L802.
[11]Aravamudan B,Thompson M,Pabelick C,et al.Brain-derived neurotrophic factor induces proliferation of human airway smooth muscle cells[J].J Cell Mol Med,2012,16:812-823.
[12]Vohra PK,Thompson MA,Sathish V,et al.TRPC3 regulates release of brain-derived neurotrophic factor from human airway smooth muscle[J].Biochim Biophys Acta,2013,1833:2953-2960.
[13]Hirota N,Martin JG.Mechanisms of airway remodeling[J].Chest,2013,144:1026-1032.
[14]Kumawat K,Koopmans T,Gosens R.β-Catenin as a regulator and therapeutic target for asthmatic airway remodeling[J].Expert opin Ther Targets,2014,18:1023-1034.
[15]Rydell-Tormanen K,Risse PA,Kanabar V,et al.Smooth muscle in tissue remodeling and hyper-reactivity:airways and arteries[J].Pulm Pharmacol Ther,2013,26:13-23.
[16]Wright DB,Meurs H,Dekkers BG.Integrins:therapeutic targets in airway hyperresponsiveness and remodeling?[J].Trends Pharmacol Sci,2014,35:567-574.
[17]Bai TR,Cooper J,Koelmeyer T,et al.The effect of age and duration of disease on airway structure in fatal asthma[J].Am J Respir Crit Care Med,2000,162:663-669.
[18]Churg A,Zhou S,Wright JL.Series“matrix metalloproteinases in lung health and disease”:Matrix metalloproteinases in Co PD[J].Eur Respir J,2012,39:197-209.
[19]Kelly EA,Jarjour NN.Role of matrix metalloproteinases in asthma[J].Curr opin Pulm Med,2003,9:28-33.
[20]Koziol-White CJ,Panettieri RA Jr.Airway smooth muscle and immunomodulation in acute exacerbations of airway disease[J].Immunol Rev,2011,242:178-185.
[21]Lagente V,Boichot E.Role of matrix metalloproteinases in the inflammatory process of respiratory diseases[J].J Mol Cell Cardiol,2010,48:440-444.
[22]ohbayashi H,Shimokata K.Matrix metalloproteinase-9 and airway remodeling in asthma[J].Curr Drug Target Inflamm Allergy,2005,4:177-181.
[23]Churg A,Zhou S,Wright JL.Series“matrix metalloproteinases in lung health and disease”:Matrix metalloproteinases in Co PD[J].Eur Respir J,2012,39:197-209.
[24]Koziol-White CJ,Panettieri RA.,Jr Airway smooth muscle and immunomodulation in acute exacerbations of airway disease[J].Immunol Rev,2011,242:178-185.
[25]Lagente V,Boichot E.Role of matrix metalloproteinases in the inflammatory process of respiratory diseases[J].J Mol Cell Cardiol,2010,48:440-444.
[26]ohbayashi H,Shimokata K.Matrix metalloproteinase-9 and airway remodeling in asthma[J].Curr Drug Targets Inflamm Allergy,2005,4:177-181.
[27]Liang KC,Lee CW,Lin WN,et al.Interleukin-1beta induces MMP-9 expression via p42/p44 MAPK,p38 MAPK,JNK,and nuclear factorkappa B signaling pathways in human tracheal smooth muscle cells[J].J Cell Physiol,2007,211:759-770.
[28]Ichimaru Y,Krimmer DI,Burgess JK,et al.TGF-βenhances deposition of perlecan from Co PD airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L325-L333.
[29]Aravamudan B,Vanoosten SK,Meuchel LW,et al.Caveolin-1 knockout mice exhibit airway hyperreactivity[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L669-L681.
[30]Possa SS,Charafeddine HT,Righetti RF,et al.Rho-kinase inhibition attenuates airway responsiveness,inflammation,matrix remodeling,and oxidative stress activation induced by chronic inflammation[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L939-L952.
[31]Marchica CL,Pinelli V,Borges M,et al.A role for decorin in a murine model of allergen-induced asthma.Am J Physiol Lung Cell Mol Physiol 300:L863-L873,2011.
[32]Kuo C,Lim S,King NJ,et al.Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and nonasthmatic airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L951-L957.
[33]Wright DB,Meurs H,Dekkers BG.Integrins:therapeutic targets in airway hyperresponsiveness and remodelling?[J].Trends Pharmacol Sci,2014,35:567-574.
[34]Ethell IM,Ethell DW.Matrix metalloproteinases in brain development and remodeling:synaptic functions and targets[J].J Neurosci Res,2007,85:2813-2823.
[35]Giblin SP,Midwood KS.Tenascin-C:Form versus function[J].Cell Adh Migr,2015,9:48-82.
[36]Mac B.Robinson,Deepak A.et al.IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle[J].American Journal of Physiology-Lung Cellular and Molecular Physiology,2015,309:2,L129-L138.
[37]Ye YL,Wu HT,Lin CF,et al.Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L216-L224.
[38]Michaeloudes C,Sukkar MB,Khorasani NM,et al.TGF-βregulates Nox4,Mn So D and catalase expression,and IL-6 release in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L295-L304.
[39]Xie S,Issa R,Sukkar MB,et al.Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells[J].Respir Res,2005,6:148.
[40]Tran T,Teoh CM,Tam JK,et al.Laminin drives survival signals to promote a contractile smooth muscle phenotype and airway hyperreactivity[J].FASEB J,2013,27:3991-4003.
[41]Possa SS,Charafeddine HT,Righetti RF,et al.Rho-kinase inhibition attenuates airway responsiveness,inflammation,matrix remodeling,and oxidative stress activation induced by chronic inflammation[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L939-L952.
[42]Bourke JE,Li X,Foster SR,et al.Collagen remodelling by airway smooth muscle is resistant to steroids and beta(2)-agonists[J].Eur Respir J,2011,37:173-182.
[43]Koziol-White CJ,Panettieri RA Jr.Airway smooth muscle and immunomodulation in acute exacerbations of airway disease[J].Immunol Rev,2011,242:178-185.
[44]Marchica CL,Pinelli V,Borges M,et al.A role for decorin in a murine model of allergen-induced asthma[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L863-L873.
[45]Sasse SK,Altonsy Mo,Kadiyala V,et al.Glucocorticoid and TNF signaling converge at A20(TNFAIP3)to repress airway smooth muscle cytokine expression[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L421-L432.
[46]Damera G,Tliba o,Panettieri RA Jr.Airway smooth muscle as an immunomodulatory cell[J].Pulm Pharmacol Ther,2009,22:353-359.
[47]Clifford RL,Patel JK,John AE,et al.CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma:regulation by BET[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L962-L972.
[48]Deacon K,Knox AJ.Human airway smooth muscle cells secrete amphiregulin via bradykinin/Co X-2/PGE2,inducing Co X-2,CXCL8,and VEGF expression in airway epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L237-L249.
[49]Faksh A,Britt RD Jr,Vogel ER,et al.TLR3 activation increases chemokine expression in human fetal airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L202-L211.
[50]Guedes AG,Jude JA,Paulin J,et al.Airway responsiveness in CD38-deficient mice in allergic airway disease:studies with bone marrow chimeras[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L485-L493.
[51]Tan X,Alrashdan YA,Alkhouri H,et al.Airway smooth muscle CXCR3ligand production:regulation by JAK-STAT1 and intracellular Ca2+[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L790-L802.
[52]Aravamudan B,Thompson MA,Pabelick CM,et al.Mechanisms of BDNF regulation in asthmatic airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L270-L279.
[53]Robinson MB,Deshpande DA,Chou J,et al.IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L129-L138.
[54]Shkumatov A,Thompson M,Choi KM,et al.Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L1125-L1135.
[55]Britt RD Jr,Faksh A,Vogel ER,et al.Vitamin D attenuates cytokineinduced remodeling in human fetal airway smooth muscle cells[J].J Cell Physiol,2015,230:1189-1198.
[56]Britt RD Jr,Thompson MA,Freeman MR,et al.Vitamin D reduces inflammation-induced contractility and remodeling of asthmatic human airway smooth muscle[J].Ann Am Thorac Soc 13,Suppl,2016,1:S97-S98.
[57]Clifford RL,Knox AJ.Vitamin D-a new treatment for airway remodelling in asthma?[J].Br J Pharmacol,2009,158:1426-1428.
[58]Kerley CP,Elnazir B,Faul J,et al.Vitamin D as an adjunctive therapy in asthma.Part 1:a review of potential mechanisms[J].Pulm Pharmacol Ther,2015,32:60-74.
[59]Brehm JM.Vitamin D and asthma-life after VIDA?[J].Curr Allergy Asthma Rep,2014,14:461.
[60]Castro M,King TS,Kunselman SJ,et al.Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels:the VIDA randomized clinical trial[J].JAMA,2014,311:2083-2091.
[61]Foong RE,Bosco A,Troy NM,et al.Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L653-L663.
[62]Mizuta K,Mizuta F,Xu D,et al.Gi-coupled gamma-aminobutyric acid-B receptors cross-regulate phospholipase C and calcium in airway smooth muscle[J].Am J Respir Cell Mol Biol,2011,45:1232-1238.
[63]Dekkers BG,Naeimi S,Bos IS,et al.l-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L301-L306.
[64]Godbole MM,Rao G,Paul BN,et al.Prenatal iodine deficiency results in structurally and functionally immature lungs in neonatal rats[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L1037-L1043.
[65]Agrawal A,Mabalirajan u,Ahmad T,et al.Emerging interface between metabolic syndrome and asthma[J].Am J Respir Cell Mol Biol,2011,44:270-275.
[66]Singh S,Bodas M,Bhatraju NK,et al.Author response to letter to editor:Hyperinsulinemia adversely affects lung structure and function[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L183-L184.
[67]Agrawal A,Prakash YS.obesity,metabolic syndrome,and airway disease:a bioenergetic problem?[J].Immunol Allergy Clin North Am,2014,34:785-796.
[68]Singh S,Bodas M,Bhatraju NK,et al.Hyperinsulinemia adversely affects lung structure and function[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L837-L845.
[69]Singh S,Prakash YS,Linneberg A,et al.Insulin and the lung:connecting asthma and metabolic syndrome[J].J Allergy(Cairo),2013,2013:627-384.
[70]Mayor RS,Finch KE,Zehr J,et al.Maternal high-fat diet is associated with impaired fetal lung development[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L360-L368.
[71]olave N,Lal CV,Halloran B,et al.Regulation of alveolar septation by micro RNA-489[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L476-L487.
[72]Che W,Manetsch M,quante T,et al.Sphingosine 1-phosphate induces MKP-1 expression via p38 MAPK-and CREB-mediated pathways in airway smooth muscle cells[J].Biochim Biophys Acta,2012,1823:1658-1665.
[73]Che W,Parmentier J,Seidel P,et al.Corticosteroids inhibit sphingosine1-phosphate-induced interleukin-6 secretion from human airway smooth muscle via mitogen-activated protein kinase phosphatase 1-mediated repression of mitogen and stress-activated protein kinase 1[J].Am J Respir Cell Mol Biol,2014,50:358-368.
[74]Rumzhum NN,Rahman MM,oliver BG,et al.Effect of sphingosine1-phosphate on cyclo-oxygenase-2 expression,prostaglandin E2 secretion,andβ2-adrenergic receptor desensitization[J].Am J Respir Cell Mol Biol,2016,54:128-135.
[75]Hallstrand TS,Wurfel MM,Lai Y,et al.Transglutaminase 2,a novel regulator of eicosanoid production in asthma revealed by genome-wide expression profiling of distinct asthma phenotypes[J].PLo S one,2010,5:e8583.
[76]Liu C,Zuo J,Pertens E,et al.Regulation of Rho/Ro CK signaling in airway smooth muscle by membrane potential and[Ca2+]i[J].Am J Physiol Lung Cell Mol Physiol,2005,289:L574-L582.
[77]Jia L,Tang DD.Abl activation regulates the dissociation of CAS from cytoskeletal vimentin by modulating CAS phosphorylation in smooth muscle[J].Am J Physiol Cell Physiol,2010,299:C630-C637.
[78]Mazzone SB,Mc Govern AE.Innervation of tracheal parasympathetic ganglia by esophageal cholinergic neurons:evidence from anatomic and functional studies in guinea pigs[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L404-L416.
[79]Rydell-Tormanen K,Risse PA,Kanabar V,et al.Smooth muscle in tissue remodeling and hyper-reactivity:airways and arteries[J].Pulm Pharmacol Ther,2013,26:13-23.
[80]Nalli AD,Kumar DP,Al-Shboul o,et al.Regulation of Gβγi-dependent PLC-β3 activity in smooth muscle:inhibitory phosphorylation of PLC-β3 by PKA and PKG and stimulatory phosphorylation of Gαi-GTPase-activating protein RGS2 by PKG[J].Cell Biochem Biophys,2014,70:867-880.
[81]Brown A,Danielsson J,Townsend EA,et al.Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L747-L758.
[82]Townsend EA,Emala CW Sr.quercetin acutely relaxes airway smooth muscle and potentiatesβ-agonist-induced relaxation via dual phosphodiesterase inhibition of PLCβand PDE4[J].Am J Physiol Lung Cell Mol Physiol,2013,305:L396-L403.
[83]Song T,Hao q,Zheng YM,et al.Inositol 1,4,5-trisphosphate activates TRPC3 channels to cause extracellular Ca2+influx in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1455-L1466.
[84]Liu q H,Zheng YM,Wang YX.Two distinct signaling pathways for regulation of spontaneous local Ca2+release by phospholipase C in airway smooth muscle cells[J].Pflügers Arch,2007,453:531-541.
[85]Croisier H,Tan X,Chen J,et al.Ryanodine receptor sensitization results in abnormal calcium signaling in airway smooth muscle cells[J].Am J Respir Cell Mol Biol,2015,53:703-711.
[86]Kasahara DI,Mathews JA,Park CY,et al.Ro CK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L736-L746.
[87]Lambert JA,Song W.ozone-induced airway hyperresponsiveness:roles of Ro CK isoforms[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1394-L1397.
[88]Bhattacharya M,Su G,Su X,et al.Iq GAP1 is necessary for pulmonary vascular barrier protection in murine acute lung injury and pneumonia[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L12-L19.
[89]Penn RB,Bond RA,Walker JK.GPCRs and arrestins in airways:implications for asthma[J].Hand Exp Pharmacol,2014,219:387-403.
[90]Pera T,Penn RB.Bronchoprotection and bronchorelaxation in asthma:New targets,and new ways to target the old ones[J].Pharmacol Ther,2016,164:82-96.
[91]Pera T,Penn RB.Crosstalk betweenβ-2-adrenoceptor and muscarinic acetylcholine receptors in the airway[J].Curr opin Pharmacol,2014,16:72-81.
[92]Wright DB,Tripathi S,Sikarwar A,et al.Regulation of GPCR-mediated smooth muscle contraction:implications for asthma and pulmonary hypertension[J].Pulm Pharmacol Ther,2013,26:121-131.
[93]Aravamudan B,Thompson MA,Pabelick CM,et al.Mechanisms of BDNF regulation in asthmatic airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L270-L279.
[94]Brandsma CA,Timens W,Jonker MR,et al.Differential effects of fluticasone on extracellular matrix production by airway and parenchymal fibroblasts in severe Co PD[J].Am J Physiol Lung Cell Mol Physiol,2013,305:L582-L589.
[95]Penn RB.Embracing emerging paradigms of G protein-coupled receptor agonism and signaling to address airway smooth muscle pathobiology in asthma[J].Naunyn Schmiedebergs Arch Pharmacol,2008,378:149-169.
[96]Siddiqui S,Redhu NS,ojo oo,et al.Emerging airway smooth muscle targets to treat asthma[J].Pulm Pharmacol Ther,2013,26:132-144.
[97]Jacobson KA.New paradigms in GPCR drug discovery[J].Biochemical pharmacology,2015,98(4):541-555.
[98]Deshpande DA,Wang WC,Mc Ilmoyle EL,et al.Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction[J].Nat Med,2010,16:1299-1304.
[99]Shaik FA,Singh N,Arakawa M,et al.Bitter taste receptors:extraoral roles in pathophysiology[J].Int J Biochem Cell Biol,2016,77:197-204.
[100]Workman AD,Palmer JN,Adappa ND,et al.The role of bitter and sweet taste receptors in upper airway immunity[J].Curr Allergy Asthma Rep,2015,15:72.
[101]Yoon SY,Shin ES,Park SY,et al.Association between polymorphisms in bitter taste receptor genes and clinical features in Korean asthmatics[J].Respiration,2016,91:141-150.
[102]Robinett KS,Deshpande DA,Malone MM,et al.Agonist-promoted homologous desensitization of human airway smooth muscle bitter taste receptors[J].Am J Respir Cell Mol Biol,2011,45:1069-1074.
[103]Pulkkinen V,Manson ML,Safholm J,et al.The bitter taste receptor(TAS2R)agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea[J].Am J Physiol Lung Cel Mol Physiol,2012,303:L956-L966.
[104]Zhang T,Luo XJ,Sai WB,et al.Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle[J].PLo S one,2014,9:e101578.
[105]Zhang CH,Lifshitz LM,uy KF,et al.The cellular and molecular basis of bitter tastant-induced bronchodilation[J].PLo S Biol,2013,11:e1001501.
[106]An SS,Wang WC,Koziol-White CJ,et al.TAS2R activation promotes airway smooth muscle relaxation despiteβ2-adrenergic receptor tachyphylaxis[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L304-L311.
[107]Kim D,Pauer SH,Yong HM,et al.β2-Adrenergic receptors chaperone trapped bitter taste receptor 14 to the cell surface as a heterodimer and exert unidirectional desensitization of taste receptor function[J].J Biol Chem,2016,291:17616-17628.
[108]Wang WC,Pauer SH,Smith DC,et al.Targeted transgenesis identifies Gαs as the bottleneck inβ2-adrenergic receptor cell signaling and physiological function in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L775-L780.
[109]Sharma P,Panebra A,Pera T,et al.Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L365-L376.
[110]Dicpinigaitis PV.Effect of the GABA-agonist baclofen on bronchial responsiveness in asthmatics[J].Pulm Pharmacol Ther,1999,12:257-260.
[111]Gallos G,Townsend E,Yim P,et al.Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L191-L197.
[112]Gallos G,Yim P,Chang S,et al.Targeting the restrictedα-subunit repertoire of airway smooth muscle GABAA receptors augments airway smooth muscle relaxation[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L248-L256.
[113]Mizuta K,osawa Y,Mizuta F,et al.Functional expression of GABAB receptors in airway epithelium[J].Am J Respir Cell Mol Biol,2008,39:296-304.
[114]Mizuta K,Mizuta F,Xu D,et al.Gi-coupledγ-aminobutyric acid-B receptors cross-regulate phospholipase C and calcium in airway smooth muscle[J].Am J Respir Cell Mol Biol,2011,45:1232-1238.
[115]Croasdell A,Thatcher TH,Kottmann RM,et al.Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L888-L901.
[116]Gallos G,Yocum GT,Siviski ME,et al.Selective targeting of theα5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L931-L942.
[117]Mizuta K,Xu D,Pan Y,et al.GABAA receptors are expressed and facilitate relaxation in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2008,294:L1206-L1216.
[118]Yocum GT,Gallos G,Zhang Y,et al.Targeting theγ-aminobutyric acid A receptorα4 subunit in airway smooth muscle to alleviate bronchoconstriction[J].Am J Respir Cell Mol Biol,2016,54:546-553.
[119]Yim PD,Gallos G,Xu D,et al.Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle[J].FASEB J,2011,25:1706-1717.
[120]Peters u,Chatterjee N,Yeager M,et al.Association of genetic variants in the calcium-sensing receptor with risk of colorectal adenoma[J].Cancer Epidemiol Biomarkers Prev,2004,13:2181-2186.
[121]Wen L,Sun L,Xi Y,et al.Expression of calcium sensing receptor and E-cadherin correlated with survival of lung adenocarcinoma[J].Thorac Cancer,2015,6:754-760.
[122]Lembrechts R,Brouns I,Schnorbusch K,et al.Functional expression of the multimodal extracellular calcium-sensing receptor in pulmonary neuroendocrine cells[J].J Cell Sci,2013,126:4490-4501.
[123]Finney BA,del Moral PM,Wilkinson WJ,et al.Regulation of mouse lung development by the extracellular calcium-sensing receptor,Ca R[J].J Physiol,2008,586:6007-6019.
[124]Kovacs CS,Kronenberg HM.Maternal-fetal calcium and bone metabolism during pregnancy,puerperium,and lactation[J].Endocr Rev,1997,18:832-872.
[125]Yarova PL,Stewart AL,Sathish V,et al.Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma[J].Sci Transl Med,2015,7:284ra260.
[126]Riccardi D,Brown EM.Physiology and pathophysiology of the calciumsensing receptor in the kidney[J].Am J Physiol Renal Physiol,2010,298:F485-F499.
[127]Riccardi D,Kemp PJ.The calcium-sensing receptor beyond extracellular calcium homeostasis:conception,development,adult physiology,and disease[J].Annu Rev Physiol,2012,74:271-297.
[128]Wenzel SE,Westcott JY,Smith HR,et al.Spectrum of prostanoid release after bronchoalveolar allergen challenge in atopic asthmatics and in control groups.An alteration in the ratio of bronchoconstrictive to bronchoprotective mediators[J].Am Rev Respir Dis,1989,139:450-457.
[129]Davi G,Basili S,Vieri M,et al.Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease.The Chronic obstructive Bronchitis and Haemostasis Study Group[J].Am J Respir Crit Care Med,1997,156:1794-1799.
[130]Allen IC,Hartney JM,Coffman TM,et al.Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism[J].Am J Physiol Lung Cell Mol Physiol,2006,290:L526-L533.
[131]Capra V,Habib A,Accomazzo MR,et al.Thromboxane prostanoid receptor in human airway smooth muscle cells:a relevant role in proliferation[J].Eur J Pharmacol,2003,474:149-159.
[132]Hernandez JM,Janssen LJ.Revisiting the usefulness of thromboxane-A2modulation in the treatment of bronchoconstriction in asthma[J].Can J Physiol Pharmacol,2015,93:111-117.
[133]Cyphert JM,Allen IC,Church RJ,et al.Allergic inflammation induces a persistent mechanistic switch in thromboxane-mediated airway constriction in the mouse[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L140-L151.
[134]Fediuk J,Gutsol A,Nolette N,Dakshinamurti S.Thromboxane-induced actin polymerization in hypoxic pulmonary artery is independent of Rho[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L13-L26.
[135]Fediuk J,Sikarwar AS,Nolette N,et al.Thromboxane-induced actin polymerization in hypoxic neonatal pulmonary arterial myocytes involves Cdc42signaling[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L877-L887.
[136]Kandhi S,qin J,Froogh G,et al.EET-dependent potentiation of pulmonary arterial pressure:sex-different regulation of soluble epoxide hydrolase[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1478-L1486.
[137]Leuchte HH,Prechtl C,Callegari J,et al.Augmentation of the effects of vasoactive intestinal peptide aerosol on pulmonary hypertension via coapplication of a neutral endopeptidase 24.11 inhibitor[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L563-L568.
[138]Shinohara M,Kibi M,Riley IR,et al.Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L746-L757.
[139]Tabet Y,Sirois M,Sirois C,et al.Relationship between bradykinin-induced relaxation and endogenous epoxyeicosanoid synthesis in human bronchi[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L562-L569.
[140]Dolan JM,Weinberg JB,o’Brien E,et al.Increased lethality and defective pulmonary clearance of Streptococcus pneumoniae in microsomal prostaglandin E synthase-1-knockout mice[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L1111-L1120.
[141]Gregory DJ,Kobzik L.Influenza lung injury:mechanisms and therapeutic opportunities[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1041-L1046.
[142]Ito Y,Correll K,Zemans RL,et al.Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling[J].Am J Physiol Lung Cel Mol Physiol,2015,308:L1178-L1188.
[143]Domingo-Gonzalez R,Wilke CA,Huang SK,et al.Transforming growth factor-βinduces micro RNA-29b to promote murine alveolar macrophage dysfunction after bone marrow transplantation[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L86-L95.
[144]ang CM,Lee IT,Chi PL,et al.TNF-αinduces cytosolic phospholipase A2expression via Jak2/PDGFR-dependent Elk-1/p300 activation in human lung epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2014,306:L543-L551.
[145]Aso H,Ito S,Mori A,et al.Prostaglandin E2 enhances interleukin-8production via EP4 receptor in human pulmonary microvascular endothelial cells[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L266-L273.
[146]Goolaerts A,Pellan-Randrianarison N,Larghero J,Vanneaux V,uzunhan Y,Gille T,Dard N,Planes C,Matthay MA,Clerici C.Conditioned media from mesenchymal stromal cells restore sodium transport and preserve epithelial permeability in an in vitro model of acute alveolar injury[J].Am J Physiol Lung Cell Mol Physiol,2014,306:L975-L985.
[147]Melboucy-Belkhir S,Pradere P,Tadbiri S,et al.Forkhead Box F1 represses cell growth and inhibits Co L1 and ARPC2 expression in lung fibroblasts in vitro[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L838-L847.
[148]Hashimoto Y,Sugiura H,Togo S,et al.27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L1028-L1041.
[149]Claar D,Hartert TV,Peebles RS Jr.The role of prostaglandins in allergic lung inflammation and asthma[J].Expert Rev Respir Med,2015,9:55-72.
[150]Aso H,Ito S,Mori A,et al.Differential regulation of airway smooth muscle cell migration by E-prostanoid receptor subtypes[J].Am J Respir Cell Mol Biol,2013,48:322-329.
[151]Benyahia C,Gomez I,Kanyinda L,et al.PGE2 receptor(EP4)agonists:potent dilators of human bronchi and future asthma therapy?[J].Pulm Pharmacol Ther,2012,25:115-118.
[152]Srivastava K,Sampson HA,Emala CW Sr,et al.The anti-asthma herbal medicine ASHMI acutely inhibits airway smooth muscle contraction via prostaglandin E2 activation of EP2/EP4 receptors[J].Am J Physiol Lung Cell Mol Physiol,2013,305:L1002-L1010.
[153]Kumawat K,Koopmans T,Gosens R.β-Catenin as a regulator and therapeutic target for asthmatic airway remodeling[J].Expert opin Ther Targets,2014,18:1023-1034.
[154]Kumawat K,Menzen MH,Bos IS,et al.Noncanonical WNT-5A signaling regulates TGF-β-induced extracellular matrix production by airway smooth muscle cells[J].FASEB J,2013,27:1631-1643.
[155]Reuter S,Beckert H,Taube C.Take the Wnt out of the inflammatory sails:modulatory effects of Wnt in airway diseases[J].Lab Invest,2016,96:177-185.
[156]Januskevicius A,Vaitkiene S,Gosens R,et al.Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma[J].BMC Pulm Med,2016,16:94.
[157]van Dijk EM,Menzen MH,Spanjer AI,et al.Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L1166-L1176.
[158]Zemans RL,Mc Clendon J,Aschner Y,et al.Role ofβ-catenin-regulated CCN matricellular proteins in epithelial repair after inflammatory lung injury[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L415-L427.
[159]Zou W,Zou Y,Zhao Z,et al.Nicotine-induced epithelial-mesenchymal transition via Wnt/β-catenin signaling in human airway epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L199-L209.
[160]Yeganeh B,Mukherjee S,Moir LM,et al.Novel non-canonical TGF-βsignaling networks:emerging roles in airway smooth muscle phenotype and function[J].Pulm Pharmacol Ther,2013,26:50-63.
[161]Maher SA,Dubuis ED,Belvisi MG.G-protein coupled receptors regulating cough[J].Curr opin Pharmacol,2011,11:248-253.
[162]Cheah EY,Burcham PC,Mann TS,et al.Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism[J].Biochem Pharmacol,2014,89:148-156.
[163]Jha A,Sharma P,Anaparti V,et al.A role for transient receptor potential ankyrin 1 cation channel(TRPA1)in airway hyper-responsiveness?[J].Can J Physiol Pharmacol,2015,93:171-176.
[164]Mitchell JE,Campbell AP,New NE,et al.Expression and characterization of the intracellular vanilloid receptor(TRPV1)in bronchi from patients with chronic cough[J].Exp Lung Res,2005,31:295-306.
[165]Watanabe N,Horie S,Spina D,et al.Immunohistochemical localization of transient receptor potential vanilloid subtype 1 in the trachea of ovalbuminsensitized Guinea pigs[J].Intl Archiv Al erg Immunol,2008,146,Suppl 1:28-32.
[166]Mc Alexander MA,Luttmann MA,Hunsberger GE,et al.Transient receptor potential vanilloid 4 activation constricts the human bronchus via the release of cysteinyl leukotrienes[J].J Pharmacol Exp Therapeut,2014,349:118-125.
[167]Zhao L,Sullivan MN,Chase M,et al.Calcineurin/nuclear factor of activated T cells-coupled vanilliod transient receptor potential channel 4Ca2+sparklets stimulate airway smooth muscle cell proliferation[J].Am J Respir Cell Mol Biol,2014,50:1064-1075.
[168]Nassini R,Pedretti P,Moretto N,et al.Transient receptor potential ankyrin1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation[J].PLo S one,2012,7:e42454.
[169]Jha A,Sharma P,Anaparti V,et al.A role for transient receptor potential ankyrin 1 cation channel(TRPA1)in airway hyper-responsiveness?[J].Can J Physiol Pharmacol,2015,93:171-176.
[170]Zhang L,An X,Wang q,et al.Activation of cold-sensitive channels TRPM8 and TRPA1 inhibits the proliferative airway smooth muscle cell phenotype[J].Lung,2016,194:595-603.
[171]Zhao L,Zhang X,Kuang H,et al.Effect of TRPV1 channel on the proliferation and apoptosis in asthmatic rat airway smooth muscle cells[J].Exp Lung Res,2013,39:283-294.
[172]Zhao LM,Kuang HY,Zhang LX,et al.Effect of TRPV1 channel on proliferation and apoptosis of airway smooth muscle cells of rats[J].J Huazhong univ Sci Technol Med Sci,2014,34:504-509.
[173]Zhao L,Sullivan MN,Chase M,et al.Calcineurin/nuclear factor of activated T cells-coupled vanilliod transient receptor potential channel 4Ca2+sparklets stimulate airway smooth muscle cell proliferation[J].Am J Respir Cell Mol Biol,2014,50:1064-1075.
[174]Mc Alexander MA,Luttmann MA,Hunsberger GE,et al.Transient receptor potential vanilloid 4 activation constricts the human bronchus via the release of cysteinyl leukotrienes[J].J Pharmacol Exp Therapeut,2014,349:118-125.
[175]Takahara N,Ito S,Furuya K,et al.Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells[J].Am J Respir Cell Mol Biol,2014,51:772-782.
[176]Faisy C,Planquette B,Naline E,et al.Acid-induced modulation of airway basal tone and contractility:role of acid-sensing ion channels(ASICs)and TRPV1 receptor[J].Life Sci,2007,81:1094-1102.
[177]Gonzalez Bosc LV,Plomaritas DR,Herbert LM,et al.ASIC1-mediated calcium entry stimulates NFATc3 nuclear translocation via PICK1 coupling in pulmonary arterial smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L48-L58.
[178]Plomaritas DR,Herbert LM,Yellowhair TR,et al.Chronic hypoxia limits H2o2-induced inhibition of ASIC1-dependent store-operated calcium entry in pulmonary arterial smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L419-L430.
[179]Ichimonji I,Tomura H,Mogi C,et al.Extracellular acidification stimulates IL-6 production and Ca2+mobilization through proton-sensing o GR1receptors in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2010,299:L567-L577.
[180]Matsuzaki S,Ishizuka T,Yamada H,et al.Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor o GR1 in human airway smooth muscle cells[J].Biochem Biophys Res Commun,2011,413:499-503.
[181]okajima F.Regulation of inflammation by extracellular acidification and proton-sensing GPCRs[J].Cell Signal,2013,25:2263-2271.
[182]Saxena H,Deshpande DA,Tiegs BC,et al.The GPCR o GR1(GPR68)mediates diverse signalling and contraction of airway smooth muscle in response to small reductions in extracellular p H[J].Br J Pharmacol,2012,166:981-990.
[183]Cook DP,Rector MV,Bouzek DC,et al.Cystic fibrosis transmembrane conductance regulator in sarcoplasmic reticulum of airway smooth muscle.Implications for airway contractility[J].Am J Respir Crit Care Med,2016,193:417-426.
[184]Michoud MC,Robert R,Hassan M,et al.Role of the cystic fibrosis transmembrane conductance channel in human airway smooth muscle[J].Am J Respir Cell Mol Biol,2009,40:217-222.
[185]Alcolado NG,Conrad DJ,Poroca D,et al.Cystic fibrosis transmembrane conductance regulator dysfunction in VIP knockout mice[J].Am J Physiol Cell Physiol,2014,307:C195-C207.
[186]Mc Cuaig S,Martin JG.How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions:implications for airway hyper-responsiveness and asthma in cystic fibrosis[J].Lancet Respir Med,2013,1:137-147.
[187]Wallace HL,Southern KW,Connell MG,et al.Abnormal tracheal smooth muscle function in the CF mouse[J].Physiol Rep,2013,1:e00138.
[188]Adam RJ,Hisert KB,Dodd JD,et al.Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities[J].JCI Insight,2016,1:e86183.
[189]Norez C,Jayle C,Becq F,Vandebrouck C.Bronchorelaxation of the human bronchi by CFTR activators[J].Pulm Pharmacol Ther,2014,27:38-43.
[190]Lin CC,Lin WN,Hou WC,et al.Endothelin-1 induces VCAM-1expression-mediated inflammation via receptor tyrosine kinases and Elk/p300 in human tracheal smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L211-L225.
[191]orlandi A,Calzetta L,Doldo E,et al.Brain natriuretic peptide modulates calcium homeostasis and epidermal growth factor receptor gene signalling in asthmatic airways smooth muscle cells[J].Pulm Pharmacol Ther,2015,31:51-54.
[192]Siddiqui S,Novali M,Tsuchiya K,et al.The modulation of large airway smooth muscle phenotype and effects of epidermal growth factor receptor inhibition in the repeatedly allergen-challenged rat[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L853-L862.
[193]Savoia CP,Liu q H,Zheng YM,et al.Calcineurin upregulates local Ca2+signaling through ryanodine receptor-1 in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L781-L790.
[194]Zhao L,Sullivan MN,Chase M,et al.Calcineurin/nuclear factor of activated T cells-coupled vanilliod transient receptor potential channel 4Ca2+sparklets stimulate airway smooth muscle cell proliferation[J].Am J Respir Cell Mol Biol,2014,50:1064-1075.
[195]Song T,Zheng YM,Vincent PA,et al.Canonical transient receptor potential3 channels activate NF-κB to mediate allergic airway disease via PKC-α/IκB-αand calcineurin/IκB-βpathways[J].FASEB J,2016,30:214-229.
[196]Klagas I,Goulet S,Karakiulakis G,et al.Decreased hyaluronan in airway smooth muscle cells from patients with asthma and Co PD[J].Eur Respir J,2009,34:616-628.
[197]Lauer ME,Cheng G,Swaidani S,et al.Tumor necrosis factor-stimulated gene-6(TSG-6)amplifies hyaluronan synthesis by airway smooth muscle cells[J].J Biol Chem,2013,288:423-431.
[198]Papakonstantinou E,Klagas I,Karakiulakis G,et al.Steroids andβ2-agonists regulate hyaluronan metabolism in asthmatic airway smooth muscle cells[J].Am J Respir Cell Mol Biol,2012,47:759-767.
[199]Garantziotis S,Brezina M,Castelnuovo P,et al.The role of hyaluronan in the pathobiology and treatment of respiratory disease[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L785-L795.
[200]Lazrak A,Creighton J,Yu Z,et al.Hyaluronan mediates airway hyperresponsiveness in oxidative lung injury[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L891-L903.
[201]Darby PJ,Kwan CY,Daniel EE.Caveolae from canine airway smooth muscle contain the necessary components for a role in Ca2+handling[J].Br J Pharmacol,2000,279:L1226-L1235.
[202]Prakash YS,Thompson MA,Vaa B,et al.Caveolins and intracellular calcium regulation in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2007,293:L1118-L1126.
[203]Gosens R,Stelmack GL,Bos ST,et al.Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells[J].J Cell Mol Med,2011,15:2430-2442.
[204]Sathish V,Abcejo AJ,Thompson MA,et al.Caveolin-1 regulation of storeoperated Ca(2+)influx in human airway smooth muscle[J].Eur Respir J,2012,40:470-478.
[205]Sathish V,Abcejo AJ,Vanoosten SK,et al.Caveolin-1 in cytokine-induced enhancement of intracellular Ca(2+)in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2011,301:L607-L614.
[206]Kc P,Martin RJ.Role of central neurotransmission and chemoreception on airway control[J].Respir Physiol Neurobiol,2010,173:213-222.
[207]undem BJ,Nassenstein C.Airway nerves and dyspnea associated with inflammatory airway disease[J].Respir Physiol Neurobiol,2009,167:36-44.
[208]Mazzone SB,Mc Govern AE.Innervation of tracheal parasympathetic ganglia by esophageal cholinergic neurons:evidence from anatomic and functional studies in guinea pigs[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L404-L416.
[209]Lieu T,Kollarik M,Myers AC,et al.Neurotrophin and GDNF family ligand receptor expression in vagal sensory nerve subtypes innervating the adult guinea pig respiratory tract[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L790-L798.
[210]Lieu TM,Myers AC,Meeker S,et al.TRPV1 induction in airway vagal lowthreshold mechanosensory neurons by allergen challenge and neurotrophic factors[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L941-L948.
[211]Meuchel LW,Stewart A,Smelter DF,et al.Neurokinin-neurotrophin interactions in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2011,301:L91-L98.
[212]Cardenas S,Scuri M,Samsell L,et al.Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs[J].Am J Physiol Lung Cell Mol Physiol,2010,299:L334-L344.
[213]Ye YL,Wu HT,Lin CF,et al.Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L216-L224.
[214]Verhein KC,Hazari MS,Moulton BC,et al.Three days after a single exposure to ozone,the mechanism of airway hyperreactivity is dependent on substance P and nerve growth factor[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L176-L184.
[215]Benayoun L,Druilhe A,Dombret MC,et al.Airway structural alterations selectively associated with severe asthma[J].Am J Respir Crit Care Med,2003,167:1360-1368.
[216]Ebina M,Takahashi T,Chiba T,Motomiya M.Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma.A 3-D morphometric study[J].Am Rev Respir Dis,1993,148:720-726.
[217]Kwak HJ,Park DW,Seo JY,et al.The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma[J].Exp Mol Medi,2015,47:e198.
[218]Bentley JK,Deng H,Linn MJ,et al.Airway smooth muscle hyperplasia and hypertrophy correlate with glycogen synthase kinase-3βphosphorylation in a mouse model of asthma[J].Am J Physiol Lung Cell Mol Physiol,2009,296:L176-L184.
[219]Ma L,Brown M,Kogut P,et al.Akt activation induces hypertrophy without contractile phenotypic maturation in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L701-L709.
[220]Mohamed JS,Lopez MA,Boriek AM.Mechanical stretch up-regulates micro RNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β[J].J Biol Chem,2010,285:29336-29347.
[221]Zhou L,Goldsmith AM,Bentley JK,et al.4E-binding protein phosphorylation and eukaryotic initiation factor-4E release are required for airway smooth muscle hypertrophy[J].Am J Respir Cell Mol Biol,2005,33:195-202.
[222]Melboucy-Belkhir S,Pradere P,Tadbiri S,et al.Forkhead Box F1 represses cell growth and inhibits Co L1 and ARPC2 expression in lung fibroblasts in vitro[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L838-L847.
[223]Goldsmith AM,Bentley JK,Zhou L,et al.Transforming growth factor-βinduces airway smooth muscle hypertrophy[J].Am J Respir Cell Mol Biol,2006,34:247-254.
[224]McWhinnie R,Pechkovsky DV,Zhou D,et al.Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2007,292:L278-L286.
[226]Peng X,Li HX,Shao HJ,et al.Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries[J].Mol Cell Biochem,2014,396:87-98.
[227]Yamamura A,Guo q,Yamamura H,et al.Enhanced Ca2+-sensing receptor function in idiopathic pulmonary arterial hypertension[J].Circ Res,2012,111:469-481.
[228]Chettimada S,Gupte R,Rawat D,et al.Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and-activation in pulmonary artery smooth muscle cells:implication in pulmonary hypertension[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L287-L300.
[230]Tang H,Chen J,Fraidenburg DR,et al.Deficiency of Akt1,but not Akt2,attenuates the development of pulmonary hypertension[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L208-L220.
[231]Trian T,Benard G,Begueret H,et al.Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma[J].J Exp Med,2007,204:3173-3181.
[232]Johnson PR,Roth M,Tamm M,et al.Airway smooth muscle cell proliferation is increased in asthma[J].Am J Respir Crit Care Med,2001,164:474-477.
[233]Trian T,Benard G,Begueret H,et al.Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma[J].J Exp Med,2007,204:3173-3181.
[234]Pieper MP,Chaudhary NI,Park JE.Acetylcholine-induced proliferation of fibroblasts and myofibroblasts in vitro is inhibited by tiotropium bromide[J].Life Sci,2007,80:2270-2273.
[235]Yahiaoui L,Villeneuve A,Valderrama-Carvajal H,et al.Endothelin-1regulates proliferative responses,both alone and synergistically with PDGF,in rat tracheal smooth muscle cells[J].Cell Physiol Biochem,2006,17:37-46.
[236]Aravamudan B,Thompson M,Pabelick C,et al.Brain-derived neurotrophic factor induces proliferation of human airway smooth muscle cells[J].J Cell Mol Med,2012,16:812-823.
[237]Dekkers BG,Maarsingh H,Meurs H,et al.Airway structural components drive airway smooth muscle remodeling in asthma[J].Proc Am Thorac Soc,2009,6:683-692.
[238]oenema TA,Mensink G,Smedinga L,et al.Cross-talk between transforming growth factor-beta(1)and muscarinic M(2)receptors augments airway smooth muscle proliferation[J].Am J Respir Cell Mol Biol,2013,49:18-27.
[239]Le Cras TD,Acciani TH,Mushaben EM,et al.Epithelial EGF receptor signaling mediates airway hyperreactivity and remodeling in a mouse model of chronic asthma[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L414-L421.
[240]Siddiqui S,Novali M,Tsuchiya K,et al.The modulation of large airway smooth muscle phenotype and effects of epidermal growth factor receptor inhibition in the repeatedly allergen-challenged rat[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L853-L862.
[241]Mc Govern T,Risse PA,Tsuchiya K,et al.LTD(4)induces HB-EGFdependent CXCL8 release through EGFR activation in human bronchial epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2010,299:L808-L815.
[242]Van Ly D,Burgess JK,Brock TG,et al.Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L239-L250.
[243]Shiomi T,Tschumperlin DJ,Park JA,et al.TNF-alpha-converting enzyme/a disintegrin and metalloprotease-17 mediates mechanotransduction in murine tracheal epithelial cells[J].Am J Respir Cell Mol Biol,2011,45:376-385.
[244]Simeone-Penney MC,Severgnini M,Rozo L,et al.PDGF-induced human airway smooth muscle cell proliferation requires STAT3 and the small GTPase Rac1[J].Am J Physiol Lung Cell Mol Physiol,2008,294:L698-L704.
[245]Clifford RL,Singer CA,John AE.Epigenetics and mi RNA emerge as key regulators of smooth muscle cell phenotype and function[J].Pulm Pharmacol Ther,2013,26:75-85.
[246]Larner-Svensson HM,Williams AE,Tsitsiou E,et al.Pharmacological studies of the mechanism and function of interleukin-1beta-induced mi RNA-146a expression in primary human airway smooth muscle[J].Respir Res,2010,11:68.
[247]Townsend EA,Miller VM,Prakash YS.Sex differences and sex steroids in lung health and disease[J].Endocr Rev,2012,33:1-47.
[248]Schuliga M,ong SC,Soon L,et al.Airway smooth muscle remodels pericellular collagen fibrils:implications for proliferation[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L584-L592.
[249]Gao YD,Zheng JW,Li P,et al.Store-operated Ca2+entry is involved in transforming growth factor-beta1 facilitated proliferation of rat airway smooth muscle cells[J].J Asthma,2013,50:439-448.
[250]Billington CK,ojo oo,Penn RB,et al.c AMP regulation of airway smooth muscle function[J].Pulm Pharmacol Ther,2013,26:112-120.
[251]Goncharova EA,Goncharov DA,Zhao H,et al.Jr beta2-adrenergic receptor agonists modulate human airway smooth muscle cell migration via vasodilator-stimulated phosphoprotein[J].Am J Respir Cell Mol Biol,2012,46:48-54.
[252]Donovan C,Tan X,Bourke JE.PPARgamma ligands regulate noncontractile and contractile functions of airway smooth muscle:implications for asthma therapy[J].PPAR Res,2012,2012:809164.
[253]Stephen J,Delvecchio C,Spitale N,et al.PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis[J].Eur Respir J,2013,41:425-432.
[254]Halwani R,Al-Abri J,Beland M,et al.CC and CXC chemokines induce airway smooth muscle proliferation and survival[J].J Immunol,2011,186:4156-4163.
[255]Ghavami S,Mutawe MM,Schaafsma D,et al.Geranylgeranyl transferase 1modulates autophagy and apoptosis in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L420-L428.
[256]Fogli S,Stefanelli F,Picchianti L,et al.Synergistic interaction between PPAR ligands and salbutamol on human bronchial smooth muscle cell proliferation[J].Br J Pharmacol,2013,168:266-275.
[257]Folinsbee LJ.Human health effects of exposure to airborne acid[J].Environ Health Perspect,1989,79:195-199.
[258]Damera G,Fogle HW,Lim P,et al.Jr Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1[J].Br J Pharmacol,2009,158:1429-1441.
[259]Bhattacharya S,Ray RM,Johnson LR.Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells[J].Apoptosis:an international journal on programmed cell death,2014,19(3):451-466.
[260]Pavlou D,Kirmizis A.Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway[J].Apoptosis,2016,21:298-311.
[261]Jyothula SS,Eissa NT.Autophagy and role in asthma[J].Curr opin Pulm Med,2013,19:30-35.
[262]Ghavami S,Mutawe MM,Schaafsma D,et al.Geranylgeranyl transferase 1modulates autophagy and apoptosis in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L420-L428.
[263]Poon A,Eidelman D,Laprise C,Hamid q.ATG5,autophagy and lung function in asthma[J].Autophagy,2012,8:694-695.
[264]Clifford RL,Patel JK,John AE,et al.CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma:regulation by BET[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L962-L972.
[265]Clifford RL,John AE,Brightling CE,et al.Abnormal histone methylation is responsible for increased vascular endothelial growth factor 165a secretion from airway smooth muscle cells in asthma[J].J Immunol,2012,189:819-831.
[266]Keslacy S,Tliba o,Baidouri H,et al.Inhibition of tumor necrosis factor-α-inducible inflammatory genes by interferon-γis associated with altered nuclear factor-κB transactivation and enhanced histone deacetylase activity[J].Mol Pharmacol,2007,71:609-618.
[267]Seidel P,Roth M,Ge q,et al.IκBαglutathionylation and reduced histone H3 phosphorylation inhibit eotaxin and RANTES[J].Eur Respir J,2011,38:1444-1452.
[268]Clarke DL,Clifford RL,Jindarat S,et al.TNFαand IFNγsynergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1,NF-κB,and the transcriptional coactivator CREBbinding protein[J].J Biol Chem,2010,285:29101-29110.
[269]Barnes PJ.Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease[J].J Allergy Clin Immunol,2013,131:636-645.
[270]Royce SG,Karagiannis TC.Histone deacetylases and their inhibitors:new implications for asthma and chronic respiratory conditions[J].Curr opin Allergy Clin Immunol,2014,14:44-48.
[271]Royce SG,Karagiannis TC.Histone deacetylases and their role in asthma[J].J Asthma,2012,49:121-128.
[272]Royce SG,Moodley Y,Samuel CS.Novel therapeutic strategies for lung disorders associated with airway remodelling and fibrosis[J].Pharmacol Therapeut,2014,141:250-260.
[273]Banerjee A,Trivedi CM,Damera G,et al.Trichostatin A abrogates airway constriction,but not inflammation,in murine and human asthma models[J].Am J Respir Cell Mol Biol,2012,46:132-138.
[274]Hou X,Wan H,Ai X,et al.Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma[J].Clin Respir J,2016,10:371-379.
[275]Royce SG,Dang W,Yuan G,et al.Effects of the histone deacetylase inhibitor,trichostatin A,in a chronic allergic airways disease model in mice[J].Arch Immunol Ther Exp(Warsz),2012,60:295-306.
[276]Toki S,Goleniewska K,Reiss S,et al.The histone deacetylase inhibitor trichostatin A suppresses murine innate allergic inflammation by blocking group 2 innate lymphoid cell(ILC2)activation[J].Thorax,2016,71:633-645.
[277]Perry MM,Durham AL,Austin PJ,et al.BET bromodomains regulate transforming growth factor-β-induced proliferation and cytokine release in asthmatic airway smooth muscle[J].J Biol Chem,2015,290:9111-9121.
[278]Nozik-Grayck E,Woods C,Stearman RS,et al.Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L124-L134.
[279]Yang S,Banerjee S,Freitas A,et al.mi R-21 regulates chronic hypoxiainduced pulmonary vascular remodeling[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L521-L529.
[280]Williams AE,Larner-Svensson H,Perry MM,et al.Micro RNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy[J].PLo S one,2009,4:e5889.
[281]Kuhn AR,Schlauch K,Lao R,et al.Micro RNA expression in human airway smooth muscle cells:role of mi R-25 in regulation of airway smooth muscle phenotype[J].Am J Respir Cell Mol Biol,2010,42:506-513.
[282]Larner-Svensson HM,Williams AE,Tsitsiou E,et al.Pharmacological studies of the mechanism and function of interleukin-1β-induced mi RNA-146a expression in primary human airway smooth muscle[J].Respir Res,2010,11:68.
[283]Comer BS,Camoretti-Mercado B,Kogut PC,et al.Micro RNA-146a and micro RNA-146b expression and anti-inflammatory function in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L727-L734.
[284]Jude JA,Dileepan M,Subramanian S,et al.mi R-140-3p regulation of TNF-α-induced CD38 expression in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L460-L468.
[285]Deshpande DA,Dileepan M,Walseth TF,et al.Micro RNA regulation of airway inflammation and airway smooth muscle function:relevance to asthma[J].Drug Dev Res,2015,76:286-295.
[286]Dileepan M,Jude JA,Rao SP,et al.Micro RNA-708 regulates CD38expression through signaling pathways JNK MAP kinase and PTEN/AKT in human airway smooth muscle cells[J].Respir Res,2014,15:107.
[287]Guedes AG,Deshpande DA,Dileepan M,et al.CD38 and airway hyperresponsiveness:studies on human airway smooth muscle cells and mouse models[J].Can J Physiol Pharmacol,2015,93:145-153.
[288]Mohamed JS,Hajira A,Li Z,et al.Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and micro RNA-26a[J].J Biol Chem,2011,286:43394-43404.
[289]Hu R,Pan W,Fedulov AV,et al.Micro RNA-10a controls airway smooth muscle cell proliferation via direct targeting of the PI3 kinase pathway[J].FASEB J,2014,28:2347-2357.
[290]Chen M,Huang L,Zhang W,et al.Mi R-23b controls TGF-β1 induced airway smooth muscle cell proliferation via TGFβR2/p-Smad3 signals[J].Mol Immunol,2016,70:84-93.
[291]Liu Y,Yang K,Sun X,et al.Mi R-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1[J].Exp Lung Res,2015,41:363-369.
[292]Liu Y,Sun X,Wu Y,et al.Effects of mi RNA-145 on airway smooth muscle cells function[J].Mol Cell Biochem,2015,409:135-143.
[293]Liao G,Panettieri RA,Tang DD.Micro RNA-203 negatively regulates c-Abl,ERK1/2 phosphorylation,and proliferation in smooth muscle cells[J].Physiol Rep,2015,3.
[294]Perry MM,Baker JE,Gibeon DS,et al.Airway smooth muscle hyperproliferation is regulated by micro RNA-221 in severe asthma[J].Am J Respir Cell Mol Biol,2014,50:7-17.
[295]Dileepan M,Jude JA,Rao SP,et al.Micro RNA-708 regulates CD38expression through signaling pathways JNK MAP kinase and PTEN/AKT in human airway smooth muscle cells[J].Respir Res,2014,15:107.
[296]Kuhn AR,Schlauch K,Lao R,et al.Micro RNA expression in human airway smooth muscle cells:role of mi R-25 in regulation of airway smooth muscle phenotype[J].Am J Respir Cell Mol Biol,2010,42:506-513.
[297]Aravamudan B,Thompson MA,Pabelick CM,et al.Mitochondria in lung diseases[J].Expert Rev Respir Med,2013,7:631-646.
[298]Contreras L,Drago I,Zampese E,et al.Mitochondria:the calcium connection[J].Biochim Biophys Acta,2010,1797:607-618.
[299]Rizzuto R,De Stefani D,Raffaello A,et al.Mitochondria as sensors and regulators of calcium signalling[J].Nat Rev Mol Cell Biol,2012,13:566-578.
[300]Aravamudan B,Thompson MA,Pabelick CM,et al.Mitochondria in lung diseases[J].Expert Rev Respir Med,2013,7:631-646.
[301]Girodet Po,Allard B,Thumerel M,et al.Bronchial smooth muscle remodeling in nonsevere asthma[J].Am J Respir Crit Care Med,2016,193:627-633.
[302]Chen T,Zhu L,Wang T,et al.Mitochondria depletion abolishes agonistinduced Ca2+plateau in airway smooth muscle cells:potential role of H2o2[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L178-L188.
[303]Michaeloudes C,Sukkar MB,Khorasani NM,et al.TGF-βregulates Nox4,Mn So D and catalase expression,and IL-6 release in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L295-L304.
[304]Aravamudan B,Thompson M,Sieck GC,et al.Functional effects of cigarette smoke-induced changes in airway smooth muscle mitochondrial morphology[J].J Cell Physiol,2017,232(5):1053-1068.
[305]Delmotte P,Sieck GC.Interaction between endoplasmic/sarcoplasmic reticulum stress(ER/SR stress),mitochondrial signaling and Ca2+regulation in airway smooth muscle(ASM)[J].Can J Physiol Pharmacol,2015,93:97-110.
[306]Delmotte P,Yang B,Thompson MA,et al.Inflammation alters regional mitochondrial Ca2+in human airway smooth muscle cells[J].Am J Physiol Cell Physiol,2012,303:C244-C256.
[307]Guo q,Li H,Liu J,et al.Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHo P signaling in a murine model of neutrophilic asthma[J].J Asthma,2017,54(2):125-133.
[308]Hsu KJ,Turvey SE.Functional analysis of the impact of o RMDL3expression on inflammation and activation of the unfolded protein response in human airway epithelial cells[J].Allergy Asthma Clin Immunol,2013,9:4.
[309]Kim SR,Lee YC.Endoplasmic reticulum stress and the related signaling networks in severe asthma[J].Allergy Asthma Immunol Res,2015,7:106-117.
[310]Lee KS,Jeong JS,Kim SR,et al.Phosphoinositide 3-kinase-δregulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress[J].Thorax,2016,71:52-63.
[311]Hoffman SM,Tully JE,Nolin JD,et al.Endoplasmic reticulum stress mediates house dust mite-induced airway epithelial apoptosis and fibrosis[J].Respir Res,2013,14:141.
[312]Makhija L,Krishnan V,Rehman R,et al.Chemical chaperones mitigate experimental asthma by attenuating endoplasmic reticulum stress[J].Am J Respir Cell Mol Biol,2014,50:923-931.
[313]Wang S,Robinet P,Smith JD,et al.o RMDL orosomucoid-like proteins are degraded by free-cholesterol-loading-induced autophagy[J].Proc Natl Acad Sci u SA,2015,112:3728-3733.
[2]Manetsch M,Seidel P,Heintz u,et al.TLR2 ligand engagement upregulates airway smooth muscle TNFα-induced cytokine production[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L838-L845.
[3]Michaeloudes C,Sukkar MB,Khorasani NM,et al.TGF-βregulates Nox4,Mn So D and catalase expression,and IL-6 release in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L295-L304.
[4]Robinson MB,Deshpande DA,Chou J,et al.IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L129-L138.
[5]Redhu NS,Gounni AS.Function and mechanisms of TSLP/TSLPR complex in asthma and Co PD[J].Clin Exp Allergy,2012,42:994-1005.
[6]Redhu NS,Saleh A,Halayko AJ,et al.Essential role of NF-κB and AP-1transcription factors in TNF-α-induced TSLP expression in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L479-L485.
[7]Baarsma HA,Menzen MH,Halayko AJ,et al.β-Catenin signaling is required for TGF-β1-induced extracellular matrix production by airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,301:L956-L965.
[8]Damera G,Tliba o,Panettieri RA.,Jr Airway smooth muscle as an immunomodulatory cell[J].Pulm Pharmacol Ther,2009,22:353-359.
[9]Alrashdan YA,Alkhouri H,Chen E,et al.Asthmatic airway smooth muscle CXCL10 production:mitogen-activated protein kinase JNK involvement[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L1118-L1127.
[10]Tan X,Alrashdan YA,Alkhouri H,et al.Airway smooth muscle CXCR3ligand production:regulation by JAK-STAT1 and intracellular Ca2+[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L790-L802.
[11]Aravamudan B,Thompson M,Pabelick C,et al.Brain-derived neurotrophic factor induces proliferation of human airway smooth muscle cells[J].J Cell Mol Med,2012,16:812-823.
[12]Vohra PK,Thompson MA,Sathish V,et al.TRPC3 regulates release of brain-derived neurotrophic factor from human airway smooth muscle[J].Biochim Biophys Acta,2013,1833:2953-2960.
[13]Hirota N,Martin JG.Mechanisms of airway remodeling[J].Chest,2013,144:1026-1032.
[14]Kumawat K,Koopmans T,Gosens R.β-Catenin as a regulator and therapeutic target for asthmatic airway remodeling[J].Expert opin Ther Targets,2014,18:1023-1034.
[15]Rydell-Tormanen K,Risse PA,Kanabar V,et al.Smooth muscle in tissue remodeling and hyper-reactivity:airways and arteries[J].Pulm Pharmacol Ther,2013,26:13-23.
[16]Wright DB,Meurs H,Dekkers BG.Integrins:therapeutic targets in airway hyperresponsiveness and remodeling?[J].Trends Pharmacol Sci,2014,35:567-574.
[17]Bai TR,Cooper J,Koelmeyer T,et al.The effect of age and duration of disease on airway structure in fatal asthma[J].Am J Respir Crit Care Med,2000,162:663-669.
[18]Churg A,Zhou S,Wright JL.Series“matrix metalloproteinases in lung health and disease”:Matrix metalloproteinases in Co PD[J].Eur Respir J,2012,39:197-209.
[19]Kelly EA,Jarjour NN.Role of matrix metalloproteinases in asthma[J].Curr opin Pulm Med,2003,9:28-33.
[20]Koziol-White CJ,Panettieri RA Jr.Airway smooth muscle and immunomodulation in acute exacerbations of airway disease[J].Immunol Rev,2011,242:178-185.
[21]Lagente V,Boichot E.Role of matrix metalloproteinases in the inflammatory process of respiratory diseases[J].J Mol Cell Cardiol,2010,48:440-444.
[22]ohbayashi H,Shimokata K.Matrix metalloproteinase-9 and airway remodeling in asthma[J].Curr Drug Target Inflamm Allergy,2005,4:177-181.
[23]Churg A,Zhou S,Wright JL.Series“matrix metalloproteinases in lung health and disease”:Matrix metalloproteinases in Co PD[J].Eur Respir J,2012,39:197-209.
[24]Koziol-White CJ,Panettieri RA.,Jr Airway smooth muscle and immunomodulation in acute exacerbations of airway disease[J].Immunol Rev,2011,242:178-185.
[25]Lagente V,Boichot E.Role of matrix metalloproteinases in the inflammatory process of respiratory diseases[J].J Mol Cell Cardiol,2010,48:440-444.
[26]ohbayashi H,Shimokata K.Matrix metalloproteinase-9 and airway remodeling in asthma[J].Curr Drug Targets Inflamm Allergy,2005,4:177-181.
[27]Liang KC,Lee CW,Lin WN,et al.Interleukin-1beta induces MMP-9 expression via p42/p44 MAPK,p38 MAPK,JNK,and nuclear factorkappa B signaling pathways in human tracheal smooth muscle cells[J].J Cell Physiol,2007,211:759-770.
[28]Ichimaru Y,Krimmer DI,Burgess JK,et al.TGF-βenhances deposition of perlecan from Co PD airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L325-L333.
[29]Aravamudan B,Vanoosten SK,Meuchel LW,et al.Caveolin-1 knockout mice exhibit airway hyperreactivity[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L669-L681.
[30]Possa SS,Charafeddine HT,Righetti RF,et al.Rho-kinase inhibition attenuates airway responsiveness,inflammation,matrix remodeling,and oxidative stress activation induced by chronic inflammation[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L939-L952.
[31]Marchica CL,Pinelli V,Borges M,et al.A role for decorin in a murine model of allergen-induced asthma.Am J Physiol Lung Cell Mol Physiol 300:L863-L873,2011.
[32]Kuo C,Lim S,King NJ,et al.Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and nonasthmatic airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L951-L957.
[33]Wright DB,Meurs H,Dekkers BG.Integrins:therapeutic targets in airway hyperresponsiveness and remodelling?[J].Trends Pharmacol Sci,2014,35:567-574.
[34]Ethell IM,Ethell DW.Matrix metalloproteinases in brain development and remodeling:synaptic functions and targets[J].J Neurosci Res,2007,85:2813-2823.
[35]Giblin SP,Midwood KS.Tenascin-C:Form versus function[J].Cell Adh Migr,2015,9:48-82.
[36]Mac B.Robinson,Deepak A.et al.IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle[J].American Journal of Physiology-Lung Cellular and Molecular Physiology,2015,309:2,L129-L138.
[37]Ye YL,Wu HT,Lin CF,et al.Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L216-L224.
[38]Michaeloudes C,Sukkar MB,Khorasani NM,et al.TGF-βregulates Nox4,Mn So D and catalase expression,and IL-6 release in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L295-L304.
[39]Xie S,Issa R,Sukkar MB,et al.Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells[J].Respir Res,2005,6:148.
[40]Tran T,Teoh CM,Tam JK,et al.Laminin drives survival signals to promote a contractile smooth muscle phenotype and airway hyperreactivity[J].FASEB J,2013,27:3991-4003.
[41]Possa SS,Charafeddine HT,Righetti RF,et al.Rho-kinase inhibition attenuates airway responsiveness,inflammation,matrix remodeling,and oxidative stress activation induced by chronic inflammation[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L939-L952.
[42]Bourke JE,Li X,Foster SR,et al.Collagen remodelling by airway smooth muscle is resistant to steroids and beta(2)-agonists[J].Eur Respir J,2011,37:173-182.
[43]Koziol-White CJ,Panettieri RA Jr.Airway smooth muscle and immunomodulation in acute exacerbations of airway disease[J].Immunol Rev,2011,242:178-185.
[44]Marchica CL,Pinelli V,Borges M,et al.A role for decorin in a murine model of allergen-induced asthma[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L863-L873.
[45]Sasse SK,Altonsy Mo,Kadiyala V,et al.Glucocorticoid and TNF signaling converge at A20(TNFAIP3)to repress airway smooth muscle cytokine expression[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L421-L432.
[46]Damera G,Tliba o,Panettieri RA Jr.Airway smooth muscle as an immunomodulatory cell[J].Pulm Pharmacol Ther,2009,22:353-359.
[47]Clifford RL,Patel JK,John AE,et al.CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma:regulation by BET[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L962-L972.
[48]Deacon K,Knox AJ.Human airway smooth muscle cells secrete amphiregulin via bradykinin/Co X-2/PGE2,inducing Co X-2,CXCL8,and VEGF expression in airway epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L237-L249.
[49]Faksh A,Britt RD Jr,Vogel ER,et al.TLR3 activation increases chemokine expression in human fetal airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L202-L211.
[50]Guedes AG,Jude JA,Paulin J,et al.Airway responsiveness in CD38-deficient mice in allergic airway disease:studies with bone marrow chimeras[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L485-L493.
[51]Tan X,Alrashdan YA,Alkhouri H,et al.Airway smooth muscle CXCR3ligand production:regulation by JAK-STAT1 and intracellular Ca2+[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L790-L802.
[52]Aravamudan B,Thompson MA,Pabelick CM,et al.Mechanisms of BDNF regulation in asthmatic airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L270-L279.
[53]Robinson MB,Deshpande DA,Chou J,et al.IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L129-L138.
[54]Shkumatov A,Thompson M,Choi KM,et al.Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L1125-L1135.
[55]Britt RD Jr,Faksh A,Vogel ER,et al.Vitamin D attenuates cytokineinduced remodeling in human fetal airway smooth muscle cells[J].J Cell Physiol,2015,230:1189-1198.
[56]Britt RD Jr,Thompson MA,Freeman MR,et al.Vitamin D reduces inflammation-induced contractility and remodeling of asthmatic human airway smooth muscle[J].Ann Am Thorac Soc 13,Suppl,2016,1:S97-S98.
[57]Clifford RL,Knox AJ.Vitamin D-a new treatment for airway remodelling in asthma?[J].Br J Pharmacol,2009,158:1426-1428.
[58]Kerley CP,Elnazir B,Faul J,et al.Vitamin D as an adjunctive therapy in asthma.Part 1:a review of potential mechanisms[J].Pulm Pharmacol Ther,2015,32:60-74.
[59]Brehm JM.Vitamin D and asthma-life after VIDA?[J].Curr Allergy Asthma Rep,2014,14:461.
[60]Castro M,King TS,Kunselman SJ,et al.Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels:the VIDA randomized clinical trial[J].JAMA,2014,311:2083-2091.
[61]Foong RE,Bosco A,Troy NM,et al.Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L653-L663.
[62]Mizuta K,Mizuta F,Xu D,et al.Gi-coupled gamma-aminobutyric acid-B receptors cross-regulate phospholipase C and calcium in airway smooth muscle[J].Am J Respir Cell Mol Biol,2011,45:1232-1238.
[63]Dekkers BG,Naeimi S,Bos IS,et al.l-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L301-L306.
[64]Godbole MM,Rao G,Paul BN,et al.Prenatal iodine deficiency results in structurally and functionally immature lungs in neonatal rats[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L1037-L1043.
[65]Agrawal A,Mabalirajan u,Ahmad T,et al.Emerging interface between metabolic syndrome and asthma[J].Am J Respir Cell Mol Biol,2011,44:270-275.
[66]Singh S,Bodas M,Bhatraju NK,et al.Author response to letter to editor:Hyperinsulinemia adversely affects lung structure and function[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L183-L184.
[67]Agrawal A,Prakash YS.obesity,metabolic syndrome,and airway disease:a bioenergetic problem?[J].Immunol Allergy Clin North Am,2014,34:785-796.
[68]Singh S,Bodas M,Bhatraju NK,et al.Hyperinsulinemia adversely affects lung structure and function[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L837-L845.
[69]Singh S,Prakash YS,Linneberg A,et al.Insulin and the lung:connecting asthma and metabolic syndrome[J].J Allergy(Cairo),2013,2013:627-384.
[70]Mayor RS,Finch KE,Zehr J,et al.Maternal high-fat diet is associated with impaired fetal lung development[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L360-L368.
[71]olave N,Lal CV,Halloran B,et al.Regulation of alveolar septation by micro RNA-489[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L476-L487.
[72]Che W,Manetsch M,quante T,et al.Sphingosine 1-phosphate induces MKP-1 expression via p38 MAPK-and CREB-mediated pathways in airway smooth muscle cells[J].Biochim Biophys Acta,2012,1823:1658-1665.
[73]Che W,Parmentier J,Seidel P,et al.Corticosteroids inhibit sphingosine1-phosphate-induced interleukin-6 secretion from human airway smooth muscle via mitogen-activated protein kinase phosphatase 1-mediated repression of mitogen and stress-activated protein kinase 1[J].Am J Respir Cell Mol Biol,2014,50:358-368.
[74]Rumzhum NN,Rahman MM,oliver BG,et al.Effect of sphingosine1-phosphate on cyclo-oxygenase-2 expression,prostaglandin E2 secretion,andβ2-adrenergic receptor desensitization[J].Am J Respir Cell Mol Biol,2016,54:128-135.
[75]Hallstrand TS,Wurfel MM,Lai Y,et al.Transglutaminase 2,a novel regulator of eicosanoid production in asthma revealed by genome-wide expression profiling of distinct asthma phenotypes[J].PLo S one,2010,5:e8583.
[76]Liu C,Zuo J,Pertens E,et al.Regulation of Rho/Ro CK signaling in airway smooth muscle by membrane potential and[Ca2+]i[J].Am J Physiol Lung Cell Mol Physiol,2005,289:L574-L582.
[77]Jia L,Tang DD.Abl activation regulates the dissociation of CAS from cytoskeletal vimentin by modulating CAS phosphorylation in smooth muscle[J].Am J Physiol Cell Physiol,2010,299:C630-C637.
[78]Mazzone SB,Mc Govern AE.Innervation of tracheal parasympathetic ganglia by esophageal cholinergic neurons:evidence from anatomic and functional studies in guinea pigs[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L404-L416.
[79]Rydell-Tormanen K,Risse PA,Kanabar V,et al.Smooth muscle in tissue remodeling and hyper-reactivity:airways and arteries[J].Pulm Pharmacol Ther,2013,26:13-23.
[80]Nalli AD,Kumar DP,Al-Shboul o,et al.Regulation of Gβγi-dependent PLC-β3 activity in smooth muscle:inhibitory phosphorylation of PLC-β3 by PKA and PKG and stimulatory phosphorylation of Gαi-GTPase-activating protein RGS2 by PKG[J].Cell Biochem Biophys,2014,70:867-880.
[81]Brown A,Danielsson J,Townsend EA,et al.Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L747-L758.
[82]Townsend EA,Emala CW Sr.quercetin acutely relaxes airway smooth muscle and potentiatesβ-agonist-induced relaxation via dual phosphodiesterase inhibition of PLCβand PDE4[J].Am J Physiol Lung Cell Mol Physiol,2013,305:L396-L403.
[83]Song T,Hao q,Zheng YM,et al.Inositol 1,4,5-trisphosphate activates TRPC3 channels to cause extracellular Ca2+influx in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1455-L1466.
[84]Liu q H,Zheng YM,Wang YX.Two distinct signaling pathways for regulation of spontaneous local Ca2+release by phospholipase C in airway smooth muscle cells[J].Pflügers Arch,2007,453:531-541.
[85]Croisier H,Tan X,Chen J,et al.Ryanodine receptor sensitization results in abnormal calcium signaling in airway smooth muscle cells[J].Am J Respir Cell Mol Biol,2015,53:703-711.
[86]Kasahara DI,Mathews JA,Park CY,et al.Ro CK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L736-L746.
[87]Lambert JA,Song W.ozone-induced airway hyperresponsiveness:roles of Ro CK isoforms[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1394-L1397.
[88]Bhattacharya M,Su G,Su X,et al.Iq GAP1 is necessary for pulmonary vascular barrier protection in murine acute lung injury and pneumonia[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L12-L19.
[89]Penn RB,Bond RA,Walker JK.GPCRs and arrestins in airways:implications for asthma[J].Hand Exp Pharmacol,2014,219:387-403.
[90]Pera T,Penn RB.Bronchoprotection and bronchorelaxation in asthma:New targets,and new ways to target the old ones[J].Pharmacol Ther,2016,164:82-96.
[91]Pera T,Penn RB.Crosstalk betweenβ-2-adrenoceptor and muscarinic acetylcholine receptors in the airway[J].Curr opin Pharmacol,2014,16:72-81.
[92]Wright DB,Tripathi S,Sikarwar A,et al.Regulation of GPCR-mediated smooth muscle contraction:implications for asthma and pulmonary hypertension[J].Pulm Pharmacol Ther,2013,26:121-131.
[93]Aravamudan B,Thompson MA,Pabelick CM,et al.Mechanisms of BDNF regulation in asthmatic airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L270-L279.
[94]Brandsma CA,Timens W,Jonker MR,et al.Differential effects of fluticasone on extracellular matrix production by airway and parenchymal fibroblasts in severe Co PD[J].Am J Physiol Lung Cell Mol Physiol,2013,305:L582-L589.
[95]Penn RB.Embracing emerging paradigms of G protein-coupled receptor agonism and signaling to address airway smooth muscle pathobiology in asthma[J].Naunyn Schmiedebergs Arch Pharmacol,2008,378:149-169.
[96]Siddiqui S,Redhu NS,ojo oo,et al.Emerging airway smooth muscle targets to treat asthma[J].Pulm Pharmacol Ther,2013,26:132-144.
[97]Jacobson KA.New paradigms in GPCR drug discovery[J].Biochemical pharmacology,2015,98(4):541-555.
[98]Deshpande DA,Wang WC,Mc Ilmoyle EL,et al.Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction[J].Nat Med,2010,16:1299-1304.
[99]Shaik FA,Singh N,Arakawa M,et al.Bitter taste receptors:extraoral roles in pathophysiology[J].Int J Biochem Cell Biol,2016,77:197-204.
[100]Workman AD,Palmer JN,Adappa ND,et al.The role of bitter and sweet taste receptors in upper airway immunity[J].Curr Allergy Asthma Rep,2015,15:72.
[101]Yoon SY,Shin ES,Park SY,et al.Association between polymorphisms in bitter taste receptor genes and clinical features in Korean asthmatics[J].Respiration,2016,91:141-150.
[102]Robinett KS,Deshpande DA,Malone MM,et al.Agonist-promoted homologous desensitization of human airway smooth muscle bitter taste receptors[J].Am J Respir Cell Mol Biol,2011,45:1069-1074.
[103]Pulkkinen V,Manson ML,Safholm J,et al.The bitter taste receptor(TAS2R)agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea[J].Am J Physiol Lung Cel Mol Physiol,2012,303:L956-L966.
[104]Zhang T,Luo XJ,Sai WB,et al.Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle[J].PLo S one,2014,9:e101578.
[105]Zhang CH,Lifshitz LM,uy KF,et al.The cellular and molecular basis of bitter tastant-induced bronchodilation[J].PLo S Biol,2013,11:e1001501.
[106]An SS,Wang WC,Koziol-White CJ,et al.TAS2R activation promotes airway smooth muscle relaxation despiteβ2-adrenergic receptor tachyphylaxis[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L304-L311.
[107]Kim D,Pauer SH,Yong HM,et al.β2-Adrenergic receptors chaperone trapped bitter taste receptor 14 to the cell surface as a heterodimer and exert unidirectional desensitization of taste receptor function[J].J Biol Chem,2016,291:17616-17628.
[108]Wang WC,Pauer SH,Smith DC,et al.Targeted transgenesis identifies Gαs as the bottleneck inβ2-adrenergic receptor cell signaling and physiological function in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L775-L780.
[109]Sharma P,Panebra A,Pera T,et al.Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L365-L376.
[110]Dicpinigaitis PV.Effect of the GABA-agonist baclofen on bronchial responsiveness in asthmatics[J].Pulm Pharmacol Ther,1999,12:257-260.
[111]Gallos G,Townsend E,Yim P,et al.Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L191-L197.
[112]Gallos G,Yim P,Chang S,et al.Targeting the restrictedα-subunit repertoire of airway smooth muscle GABAA receptors augments airway smooth muscle relaxation[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L248-L256.
[113]Mizuta K,osawa Y,Mizuta F,et al.Functional expression of GABAB receptors in airway epithelium[J].Am J Respir Cell Mol Biol,2008,39:296-304.
[114]Mizuta K,Mizuta F,Xu D,et al.Gi-coupledγ-aminobutyric acid-B receptors cross-regulate phospholipase C and calcium in airway smooth muscle[J].Am J Respir Cell Mol Biol,2011,45:1232-1238.
[115]Croasdell A,Thatcher TH,Kottmann RM,et al.Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L888-L901.
[116]Gallos G,Yocum GT,Siviski ME,et al.Selective targeting of theα5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L931-L942.
[117]Mizuta K,Xu D,Pan Y,et al.GABAA receptors are expressed and facilitate relaxation in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2008,294:L1206-L1216.
[118]Yocum GT,Gallos G,Zhang Y,et al.Targeting theγ-aminobutyric acid A receptorα4 subunit in airway smooth muscle to alleviate bronchoconstriction[J].Am J Respir Cell Mol Biol,2016,54:546-553.
[119]Yim PD,Gallos G,Xu D,et al.Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle[J].FASEB J,2011,25:1706-1717.
[120]Peters u,Chatterjee N,Yeager M,et al.Association of genetic variants in the calcium-sensing receptor with risk of colorectal adenoma[J].Cancer Epidemiol Biomarkers Prev,2004,13:2181-2186.
[121]Wen L,Sun L,Xi Y,et al.Expression of calcium sensing receptor and E-cadherin correlated with survival of lung adenocarcinoma[J].Thorac Cancer,2015,6:754-760.
[122]Lembrechts R,Brouns I,Schnorbusch K,et al.Functional expression of the multimodal extracellular calcium-sensing receptor in pulmonary neuroendocrine cells[J].J Cell Sci,2013,126:4490-4501.
[123]Finney BA,del Moral PM,Wilkinson WJ,et al.Regulation of mouse lung development by the extracellular calcium-sensing receptor,Ca R[J].J Physiol,2008,586:6007-6019.
[124]Kovacs CS,Kronenberg HM.Maternal-fetal calcium and bone metabolism during pregnancy,puerperium,and lactation[J].Endocr Rev,1997,18:832-872.
[125]Yarova PL,Stewart AL,Sathish V,et al.Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma[J].Sci Transl Med,2015,7:284ra260.
[126]Riccardi D,Brown EM.Physiology and pathophysiology of the calciumsensing receptor in the kidney[J].Am J Physiol Renal Physiol,2010,298:F485-F499.
[127]Riccardi D,Kemp PJ.The calcium-sensing receptor beyond extracellular calcium homeostasis:conception,development,adult physiology,and disease[J].Annu Rev Physiol,2012,74:271-297.
[128]Wenzel SE,Westcott JY,Smith HR,et al.Spectrum of prostanoid release after bronchoalveolar allergen challenge in atopic asthmatics and in control groups.An alteration in the ratio of bronchoconstrictive to bronchoprotective mediators[J].Am Rev Respir Dis,1989,139:450-457.
[129]Davi G,Basili S,Vieri M,et al.Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease.The Chronic obstructive Bronchitis and Haemostasis Study Group[J].Am J Respir Crit Care Med,1997,156:1794-1799.
[130]Allen IC,Hartney JM,Coffman TM,et al.Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism[J].Am J Physiol Lung Cell Mol Physiol,2006,290:L526-L533.
[131]Capra V,Habib A,Accomazzo MR,et al.Thromboxane prostanoid receptor in human airway smooth muscle cells:a relevant role in proliferation[J].Eur J Pharmacol,2003,474:149-159.
[132]Hernandez JM,Janssen LJ.Revisiting the usefulness of thromboxane-A2modulation in the treatment of bronchoconstriction in asthma[J].Can J Physiol Pharmacol,2015,93:111-117.
[133]Cyphert JM,Allen IC,Church RJ,et al.Allergic inflammation induces a persistent mechanistic switch in thromboxane-mediated airway constriction in the mouse[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L140-L151.
[134]Fediuk J,Gutsol A,Nolette N,Dakshinamurti S.Thromboxane-induced actin polymerization in hypoxic pulmonary artery is independent of Rho[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L13-L26.
[135]Fediuk J,Sikarwar AS,Nolette N,et al.Thromboxane-induced actin polymerization in hypoxic neonatal pulmonary arterial myocytes involves Cdc42signaling[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L877-L887.
[136]Kandhi S,qin J,Froogh G,et al.EET-dependent potentiation of pulmonary arterial pressure:sex-different regulation of soluble epoxide hydrolase[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1478-L1486.
[137]Leuchte HH,Prechtl C,Callegari J,et al.Augmentation of the effects of vasoactive intestinal peptide aerosol on pulmonary hypertension via coapplication of a neutral endopeptidase 24.11 inhibitor[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L563-L568.
[138]Shinohara M,Kibi M,Riley IR,et al.Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L746-L757.
[139]Tabet Y,Sirois M,Sirois C,et al.Relationship between bradykinin-induced relaxation and endogenous epoxyeicosanoid synthesis in human bronchi[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L562-L569.
[140]Dolan JM,Weinberg JB,o’Brien E,et al.Increased lethality and defective pulmonary clearance of Streptococcus pneumoniae in microsomal prostaglandin E synthase-1-knockout mice[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L1111-L1120.
[141]Gregory DJ,Kobzik L.Influenza lung injury:mechanisms and therapeutic opportunities[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L1041-L1046.
[142]Ito Y,Correll K,Zemans RL,et al.Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling[J].Am J Physiol Lung Cel Mol Physiol,2015,308:L1178-L1188.
[143]Domingo-Gonzalez R,Wilke CA,Huang SK,et al.Transforming growth factor-βinduces micro RNA-29b to promote murine alveolar macrophage dysfunction after bone marrow transplantation[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L86-L95.
[144]ang CM,Lee IT,Chi PL,et al.TNF-αinduces cytosolic phospholipase A2expression via Jak2/PDGFR-dependent Elk-1/p300 activation in human lung epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2014,306:L543-L551.
[145]Aso H,Ito S,Mori A,et al.Prostaglandin E2 enhances interleukin-8production via EP4 receptor in human pulmonary microvascular endothelial cells[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L266-L273.
[146]Goolaerts A,Pellan-Randrianarison N,Larghero J,Vanneaux V,uzunhan Y,Gille T,Dard N,Planes C,Matthay MA,Clerici C.Conditioned media from mesenchymal stromal cells restore sodium transport and preserve epithelial permeability in an in vitro model of acute alveolar injury[J].Am J Physiol Lung Cell Mol Physiol,2014,306:L975-L985.
[147]Melboucy-Belkhir S,Pradere P,Tadbiri S,et al.Forkhead Box F1 represses cell growth and inhibits Co L1 and ARPC2 expression in lung fibroblasts in vitro[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L838-L847.
[148]Hashimoto Y,Sugiura H,Togo S,et al.27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L1028-L1041.
[149]Claar D,Hartert TV,Peebles RS Jr.The role of prostaglandins in allergic lung inflammation and asthma[J].Expert Rev Respir Med,2015,9:55-72.
[150]Aso H,Ito S,Mori A,et al.Differential regulation of airway smooth muscle cell migration by E-prostanoid receptor subtypes[J].Am J Respir Cell Mol Biol,2013,48:322-329.
[151]Benyahia C,Gomez I,Kanyinda L,et al.PGE2 receptor(EP4)agonists:potent dilators of human bronchi and future asthma therapy?[J].Pulm Pharmacol Ther,2012,25:115-118.
[152]Srivastava K,Sampson HA,Emala CW Sr,et al.The anti-asthma herbal medicine ASHMI acutely inhibits airway smooth muscle contraction via prostaglandin E2 activation of EP2/EP4 receptors[J].Am J Physiol Lung Cell Mol Physiol,2013,305:L1002-L1010.
[153]Kumawat K,Koopmans T,Gosens R.β-Catenin as a regulator and therapeutic target for asthmatic airway remodeling[J].Expert opin Ther Targets,2014,18:1023-1034.
[154]Kumawat K,Menzen MH,Bos IS,et al.Noncanonical WNT-5A signaling regulates TGF-β-induced extracellular matrix production by airway smooth muscle cells[J].FASEB J,2013,27:1631-1643.
[155]Reuter S,Beckert H,Taube C.Take the Wnt out of the inflammatory sails:modulatory effects of Wnt in airway diseases[J].Lab Invest,2016,96:177-185.
[156]Januskevicius A,Vaitkiene S,Gosens R,et al.Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma[J].BMC Pulm Med,2016,16:94.
[157]van Dijk EM,Menzen MH,Spanjer AI,et al.Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L1166-L1176.
[158]Zemans RL,Mc Clendon J,Aschner Y,et al.Role ofβ-catenin-regulated CCN matricellular proteins in epithelial repair after inflammatory lung injury[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L415-L427.
[159]Zou W,Zou Y,Zhao Z,et al.Nicotine-induced epithelial-mesenchymal transition via Wnt/β-catenin signaling in human airway epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L199-L209.
[160]Yeganeh B,Mukherjee S,Moir LM,et al.Novel non-canonical TGF-βsignaling networks:emerging roles in airway smooth muscle phenotype and function[J].Pulm Pharmacol Ther,2013,26:50-63.
[161]Maher SA,Dubuis ED,Belvisi MG.G-protein coupled receptors regulating cough[J].Curr opin Pharmacol,2011,11:248-253.
[162]Cheah EY,Burcham PC,Mann TS,et al.Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism[J].Biochem Pharmacol,2014,89:148-156.
[163]Jha A,Sharma P,Anaparti V,et al.A role for transient receptor potential ankyrin 1 cation channel(TRPA1)in airway hyper-responsiveness?[J].Can J Physiol Pharmacol,2015,93:171-176.
[164]Mitchell JE,Campbell AP,New NE,et al.Expression and characterization of the intracellular vanilloid receptor(TRPV1)in bronchi from patients with chronic cough[J].Exp Lung Res,2005,31:295-306.
[165]Watanabe N,Horie S,Spina D,et al.Immunohistochemical localization of transient receptor potential vanilloid subtype 1 in the trachea of ovalbuminsensitized Guinea pigs[J].Intl Archiv Al erg Immunol,2008,146,Suppl 1:28-32.
[166]Mc Alexander MA,Luttmann MA,Hunsberger GE,et al.Transient receptor potential vanilloid 4 activation constricts the human bronchus via the release of cysteinyl leukotrienes[J].J Pharmacol Exp Therapeut,2014,349:118-125.
[167]Zhao L,Sullivan MN,Chase M,et al.Calcineurin/nuclear factor of activated T cells-coupled vanilliod transient receptor potential channel 4Ca2+sparklets stimulate airway smooth muscle cell proliferation[J].Am J Respir Cell Mol Biol,2014,50:1064-1075.
[168]Nassini R,Pedretti P,Moretto N,et al.Transient receptor potential ankyrin1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation[J].PLo S one,2012,7:e42454.
[169]Jha A,Sharma P,Anaparti V,et al.A role for transient receptor potential ankyrin 1 cation channel(TRPA1)in airway hyper-responsiveness?[J].Can J Physiol Pharmacol,2015,93:171-176.
[170]Zhang L,An X,Wang q,et al.Activation of cold-sensitive channels TRPM8 and TRPA1 inhibits the proliferative airway smooth muscle cell phenotype[J].Lung,2016,194:595-603.
[171]Zhao L,Zhang X,Kuang H,et al.Effect of TRPV1 channel on the proliferation and apoptosis in asthmatic rat airway smooth muscle cells[J].Exp Lung Res,2013,39:283-294.
[172]Zhao LM,Kuang HY,Zhang LX,et al.Effect of TRPV1 channel on proliferation and apoptosis of airway smooth muscle cells of rats[J].J Huazhong univ Sci Technol Med Sci,2014,34:504-509.
[173]Zhao L,Sullivan MN,Chase M,et al.Calcineurin/nuclear factor of activated T cells-coupled vanilliod transient receptor potential channel 4Ca2+sparklets stimulate airway smooth muscle cell proliferation[J].Am J Respir Cell Mol Biol,2014,50:1064-1075.
[174]Mc Alexander MA,Luttmann MA,Hunsberger GE,et al.Transient receptor potential vanilloid 4 activation constricts the human bronchus via the release of cysteinyl leukotrienes[J].J Pharmacol Exp Therapeut,2014,349:118-125.
[175]Takahara N,Ito S,Furuya K,et al.Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells[J].Am J Respir Cell Mol Biol,2014,51:772-782.
[176]Faisy C,Planquette B,Naline E,et al.Acid-induced modulation of airway basal tone and contractility:role of acid-sensing ion channels(ASICs)and TRPV1 receptor[J].Life Sci,2007,81:1094-1102.
[177]Gonzalez Bosc LV,Plomaritas DR,Herbert LM,et al.ASIC1-mediated calcium entry stimulates NFATc3 nuclear translocation via PICK1 coupling in pulmonary arterial smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L48-L58.
[178]Plomaritas DR,Herbert LM,Yellowhair TR,et al.Chronic hypoxia limits H2o2-induced inhibition of ASIC1-dependent store-operated calcium entry in pulmonary arterial smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L419-L430.
[179]Ichimonji I,Tomura H,Mogi C,et al.Extracellular acidification stimulates IL-6 production and Ca2+mobilization through proton-sensing o GR1receptors in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2010,299:L567-L577.
[180]Matsuzaki S,Ishizuka T,Yamada H,et al.Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor o GR1 in human airway smooth muscle cells[J].Biochem Biophys Res Commun,2011,413:499-503.
[181]okajima F.Regulation of inflammation by extracellular acidification and proton-sensing GPCRs[J].Cell Signal,2013,25:2263-2271.
[182]Saxena H,Deshpande DA,Tiegs BC,et al.The GPCR o GR1(GPR68)mediates diverse signalling and contraction of airway smooth muscle in response to small reductions in extracellular p H[J].Br J Pharmacol,2012,166:981-990.
[183]Cook DP,Rector MV,Bouzek DC,et al.Cystic fibrosis transmembrane conductance regulator in sarcoplasmic reticulum of airway smooth muscle.Implications for airway contractility[J].Am J Respir Crit Care Med,2016,193:417-426.
[184]Michoud MC,Robert R,Hassan M,et al.Role of the cystic fibrosis transmembrane conductance channel in human airway smooth muscle[J].Am J Respir Cell Mol Biol,2009,40:217-222.
[185]Alcolado NG,Conrad DJ,Poroca D,et al.Cystic fibrosis transmembrane conductance regulator dysfunction in VIP knockout mice[J].Am J Physiol Cell Physiol,2014,307:C195-C207.
[186]Mc Cuaig S,Martin JG.How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions:implications for airway hyper-responsiveness and asthma in cystic fibrosis[J].Lancet Respir Med,2013,1:137-147.
[187]Wallace HL,Southern KW,Connell MG,et al.Abnormal tracheal smooth muscle function in the CF mouse[J].Physiol Rep,2013,1:e00138.
[188]Adam RJ,Hisert KB,Dodd JD,et al.Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities[J].JCI Insight,2016,1:e86183.
[189]Norez C,Jayle C,Becq F,Vandebrouck C.Bronchorelaxation of the human bronchi by CFTR activators[J].Pulm Pharmacol Ther,2014,27:38-43.
[190]Lin CC,Lin WN,Hou WC,et al.Endothelin-1 induces VCAM-1expression-mediated inflammation via receptor tyrosine kinases and Elk/p300 in human tracheal smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2015,309:L211-L225.
[191]orlandi A,Calzetta L,Doldo E,et al.Brain natriuretic peptide modulates calcium homeostasis and epidermal growth factor receptor gene signalling in asthmatic airways smooth muscle cells[J].Pulm Pharmacol Ther,2015,31:51-54.
[192]Siddiqui S,Novali M,Tsuchiya K,et al.The modulation of large airway smooth muscle phenotype and effects of epidermal growth factor receptor inhibition in the repeatedly allergen-challenged rat[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L853-L862.
[193]Savoia CP,Liu q H,Zheng YM,et al.Calcineurin upregulates local Ca2+signaling through ryanodine receptor-1 in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L781-L790.
[194]Zhao L,Sullivan MN,Chase M,et al.Calcineurin/nuclear factor of activated T cells-coupled vanilliod transient receptor potential channel 4Ca2+sparklets stimulate airway smooth muscle cell proliferation[J].Am J Respir Cell Mol Biol,2014,50:1064-1075.
[195]Song T,Zheng YM,Vincent PA,et al.Canonical transient receptor potential3 channels activate NF-κB to mediate allergic airway disease via PKC-α/IκB-αand calcineurin/IκB-βpathways[J].FASEB J,2016,30:214-229.
[196]Klagas I,Goulet S,Karakiulakis G,et al.Decreased hyaluronan in airway smooth muscle cells from patients with asthma and Co PD[J].Eur Respir J,2009,34:616-628.
[197]Lauer ME,Cheng G,Swaidani S,et al.Tumor necrosis factor-stimulated gene-6(TSG-6)amplifies hyaluronan synthesis by airway smooth muscle cells[J].J Biol Chem,2013,288:423-431.
[198]Papakonstantinou E,Klagas I,Karakiulakis G,et al.Steroids andβ2-agonists regulate hyaluronan metabolism in asthmatic airway smooth muscle cells[J].Am J Respir Cell Mol Biol,2012,47:759-767.
[199]Garantziotis S,Brezina M,Castelnuovo P,et al.The role of hyaluronan in the pathobiology and treatment of respiratory disease[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L785-L795.
[200]Lazrak A,Creighton J,Yu Z,et al.Hyaluronan mediates airway hyperresponsiveness in oxidative lung injury[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L891-L903.
[201]Darby PJ,Kwan CY,Daniel EE.Caveolae from canine airway smooth muscle contain the necessary components for a role in Ca2+handling[J].Br J Pharmacol,2000,279:L1226-L1235.
[202]Prakash YS,Thompson MA,Vaa B,et al.Caveolins and intracellular calcium regulation in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2007,293:L1118-L1126.
[203]Gosens R,Stelmack GL,Bos ST,et al.Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells[J].J Cell Mol Med,2011,15:2430-2442.
[204]Sathish V,Abcejo AJ,Thompson MA,et al.Caveolin-1 regulation of storeoperated Ca(2+)influx in human airway smooth muscle[J].Eur Respir J,2012,40:470-478.
[205]Sathish V,Abcejo AJ,Vanoosten SK,et al.Caveolin-1 in cytokine-induced enhancement of intracellular Ca(2+)in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2011,301:L607-L614.
[206]Kc P,Martin RJ.Role of central neurotransmission and chemoreception on airway control[J].Respir Physiol Neurobiol,2010,173:213-222.
[207]undem BJ,Nassenstein C.Airway nerves and dyspnea associated with inflammatory airway disease[J].Respir Physiol Neurobiol,2009,167:36-44.
[208]Mazzone SB,Mc Govern AE.Innervation of tracheal parasympathetic ganglia by esophageal cholinergic neurons:evidence from anatomic and functional studies in guinea pigs[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L404-L416.
[209]Lieu T,Kollarik M,Myers AC,et al.Neurotrophin and GDNF family ligand receptor expression in vagal sensory nerve subtypes innervating the adult guinea pig respiratory tract[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L790-L798.
[210]Lieu TM,Myers AC,Meeker S,et al.TRPV1 induction in airway vagal lowthreshold mechanosensory neurons by allergen challenge and neurotrophic factors[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L941-L948.
[211]Meuchel LW,Stewart A,Smelter DF,et al.Neurokinin-neurotrophin interactions in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2011,301:L91-L98.
[212]Cardenas S,Scuri M,Samsell L,et al.Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs[J].Am J Physiol Lung Cell Mol Physiol,2010,299:L334-L344.
[213]Ye YL,Wu HT,Lin CF,et al.Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L216-L224.
[214]Verhein KC,Hazari MS,Moulton BC,et al.Three days after a single exposure to ozone,the mechanism of airway hyperreactivity is dependent on substance P and nerve growth factor[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L176-L184.
[215]Benayoun L,Druilhe A,Dombret MC,et al.Airway structural alterations selectively associated with severe asthma[J].Am J Respir Crit Care Med,2003,167:1360-1368.
[216]Ebina M,Takahashi T,Chiba T,Motomiya M.Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma.A 3-D morphometric study[J].Am Rev Respir Dis,1993,148:720-726.
[217]Kwak HJ,Park DW,Seo JY,et al.The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma[J].Exp Mol Medi,2015,47:e198.
[218]Bentley JK,Deng H,Linn MJ,et al.Airway smooth muscle hyperplasia and hypertrophy correlate with glycogen synthase kinase-3βphosphorylation in a mouse model of asthma[J].Am J Physiol Lung Cell Mol Physiol,2009,296:L176-L184.
[219]Ma L,Brown M,Kogut P,et al.Akt activation induces hypertrophy without contractile phenotypic maturation in airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L701-L709.
[220]Mohamed JS,Lopez MA,Boriek AM.Mechanical stretch up-regulates micro RNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3β[J].J Biol Chem,2010,285:29336-29347.
[221]Zhou L,Goldsmith AM,Bentley JK,et al.4E-binding protein phosphorylation and eukaryotic initiation factor-4E release are required for airway smooth muscle hypertrophy[J].Am J Respir Cell Mol Biol,2005,33:195-202.
[222]Melboucy-Belkhir S,Pradere P,Tadbiri S,et al.Forkhead Box F1 represses cell growth and inhibits Co L1 and ARPC2 expression in lung fibroblasts in vitro[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L838-L847.
[223]Goldsmith AM,Bentley JK,Zhou L,et al.Transforming growth factor-βinduces airway smooth muscle hypertrophy[J].Am J Respir Cell Mol Biol,2006,34:247-254.
[224]McWhinnie R,Pechkovsky DV,Zhou D,et al.Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2007,292:L278-L286.
[226]Peng X,Li HX,Shao HJ,et al.Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries[J].Mol Cell Biochem,2014,396:87-98.
[227]Yamamura A,Guo q,Yamamura H,et al.Enhanced Ca2+-sensing receptor function in idiopathic pulmonary arterial hypertension[J].Circ Res,2012,111:469-481.
[228]Chettimada S,Gupte R,Rawat D,et al.Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and-activation in pulmonary artery smooth muscle cells:implication in pulmonary hypertension[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L287-L300.
[230]Tang H,Chen J,Fraidenburg DR,et al.Deficiency of Akt1,but not Akt2,attenuates the development of pulmonary hypertension[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L208-L220.
[231]Trian T,Benard G,Begueret H,et al.Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma[J].J Exp Med,2007,204:3173-3181.
[232]Johnson PR,Roth M,Tamm M,et al.Airway smooth muscle cell proliferation is increased in asthma[J].Am J Respir Crit Care Med,2001,164:474-477.
[233]Trian T,Benard G,Begueret H,et al.Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma[J].J Exp Med,2007,204:3173-3181.
[234]Pieper MP,Chaudhary NI,Park JE.Acetylcholine-induced proliferation of fibroblasts and myofibroblasts in vitro is inhibited by tiotropium bromide[J].Life Sci,2007,80:2270-2273.
[235]Yahiaoui L,Villeneuve A,Valderrama-Carvajal H,et al.Endothelin-1regulates proliferative responses,both alone and synergistically with PDGF,in rat tracheal smooth muscle cells[J].Cell Physiol Biochem,2006,17:37-46.
[236]Aravamudan B,Thompson M,Pabelick C,et al.Brain-derived neurotrophic factor induces proliferation of human airway smooth muscle cells[J].J Cell Mol Med,2012,16:812-823.
[237]Dekkers BG,Maarsingh H,Meurs H,et al.Airway structural components drive airway smooth muscle remodeling in asthma[J].Proc Am Thorac Soc,2009,6:683-692.
[238]oenema TA,Mensink G,Smedinga L,et al.Cross-talk between transforming growth factor-beta(1)and muscarinic M(2)receptors augments airway smooth muscle proliferation[J].Am J Respir Cell Mol Biol,2013,49:18-27.
[239]Le Cras TD,Acciani TH,Mushaben EM,et al.Epithelial EGF receptor signaling mediates airway hyperreactivity and remodeling in a mouse model of chronic asthma[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L414-L421.
[240]Siddiqui S,Novali M,Tsuchiya K,et al.The modulation of large airway smooth muscle phenotype and effects of epidermal growth factor receptor inhibition in the repeatedly allergen-challenged rat[J].Am J Physiol Lung Cell Mol Physiol,2013,304:L853-L862.
[241]Mc Govern T,Risse PA,Tsuchiya K,et al.LTD(4)induces HB-EGFdependent CXCL8 release through EGFR activation in human bronchial epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2010,299:L808-L815.
[242]Van Ly D,Burgess JK,Brock TG,et al.Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L239-L250.
[243]Shiomi T,Tschumperlin DJ,Park JA,et al.TNF-alpha-converting enzyme/a disintegrin and metalloprotease-17 mediates mechanotransduction in murine tracheal epithelial cells[J].Am J Respir Cell Mol Biol,2011,45:376-385.
[244]Simeone-Penney MC,Severgnini M,Rozo L,et al.PDGF-induced human airway smooth muscle cell proliferation requires STAT3 and the small GTPase Rac1[J].Am J Physiol Lung Cell Mol Physiol,2008,294:L698-L704.
[245]Clifford RL,Singer CA,John AE.Epigenetics and mi RNA emerge as key regulators of smooth muscle cell phenotype and function[J].Pulm Pharmacol Ther,2013,26:75-85.
[246]Larner-Svensson HM,Williams AE,Tsitsiou E,et al.Pharmacological studies of the mechanism and function of interleukin-1beta-induced mi RNA-146a expression in primary human airway smooth muscle[J].Respir Res,2010,11:68.
[247]Townsend EA,Miller VM,Prakash YS.Sex differences and sex steroids in lung health and disease[J].Endocr Rev,2012,33:1-47.
[248]Schuliga M,ong SC,Soon L,et al.Airway smooth muscle remodels pericellular collagen fibrils:implications for proliferation[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L584-L592.
[249]Gao YD,Zheng JW,Li P,et al.Store-operated Ca2+entry is involved in transforming growth factor-beta1 facilitated proliferation of rat airway smooth muscle cells[J].J Asthma,2013,50:439-448.
[250]Billington CK,ojo oo,Penn RB,et al.c AMP regulation of airway smooth muscle function[J].Pulm Pharmacol Ther,2013,26:112-120.
[251]Goncharova EA,Goncharov DA,Zhao H,et al.Jr beta2-adrenergic receptor agonists modulate human airway smooth muscle cell migration via vasodilator-stimulated phosphoprotein[J].Am J Respir Cell Mol Biol,2012,46:48-54.
[252]Donovan C,Tan X,Bourke JE.PPARgamma ligands regulate noncontractile and contractile functions of airway smooth muscle:implications for asthma therapy[J].PPAR Res,2012,2012:809164.
[253]Stephen J,Delvecchio C,Spitale N,et al.PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis[J].Eur Respir J,2013,41:425-432.
[254]Halwani R,Al-Abri J,Beland M,et al.CC and CXC chemokines induce airway smooth muscle proliferation and survival[J].J Immunol,2011,186:4156-4163.
[255]Ghavami S,Mutawe MM,Schaafsma D,et al.Geranylgeranyl transferase 1modulates autophagy and apoptosis in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L420-L428.
[256]Fogli S,Stefanelli F,Picchianti L,et al.Synergistic interaction between PPAR ligands and salbutamol on human bronchial smooth muscle cell proliferation[J].Br J Pharmacol,2013,168:266-275.
[257]Folinsbee LJ.Human health effects of exposure to airborne acid[J].Environ Health Perspect,1989,79:195-199.
[258]Damera G,Fogle HW,Lim P,et al.Jr Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1[J].Br J Pharmacol,2009,158:1429-1441.
[259]Bhattacharya S,Ray RM,Johnson LR.Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells[J].Apoptosis:an international journal on programmed cell death,2014,19(3):451-466.
[260]Pavlou D,Kirmizis A.Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway[J].Apoptosis,2016,21:298-311.
[261]Jyothula SS,Eissa NT.Autophagy and role in asthma[J].Curr opin Pulm Med,2013,19:30-35.
[262]Ghavami S,Mutawe MM,Schaafsma D,et al.Geranylgeranyl transferase 1modulates autophagy and apoptosis in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L420-L428.
[263]Poon A,Eidelman D,Laprise C,Hamid q.ATG5,autophagy and lung function in asthma[J].Autophagy,2012,8:694-695.
[264]Clifford RL,Patel JK,John AE,et al.CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma:regulation by BET[J].Am J Physiol Lung Cell Mol Physiol,2015,308:L962-L972.
[265]Clifford RL,John AE,Brightling CE,et al.Abnormal histone methylation is responsible for increased vascular endothelial growth factor 165a secretion from airway smooth muscle cells in asthma[J].J Immunol,2012,189:819-831.
[266]Keslacy S,Tliba o,Baidouri H,et al.Inhibition of tumor necrosis factor-α-inducible inflammatory genes by interferon-γis associated with altered nuclear factor-κB transactivation and enhanced histone deacetylase activity[J].Mol Pharmacol,2007,71:609-618.
[267]Seidel P,Roth M,Ge q,et al.IκBαglutathionylation and reduced histone H3 phosphorylation inhibit eotaxin and RANTES[J].Eur Respir J,2011,38:1444-1452.
[268]Clarke DL,Clifford RL,Jindarat S,et al.TNFαand IFNγsynergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1,NF-κB,and the transcriptional coactivator CREBbinding protein[J].J Biol Chem,2010,285:29101-29110.
[269]Barnes PJ.Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease[J].J Allergy Clin Immunol,2013,131:636-645.
[270]Royce SG,Karagiannis TC.Histone deacetylases and their inhibitors:new implications for asthma and chronic respiratory conditions[J].Curr opin Allergy Clin Immunol,2014,14:44-48.
[271]Royce SG,Karagiannis TC.Histone deacetylases and their role in asthma[J].J Asthma,2012,49:121-128.
[272]Royce SG,Moodley Y,Samuel CS.Novel therapeutic strategies for lung disorders associated with airway remodelling and fibrosis[J].Pharmacol Therapeut,2014,141:250-260.
[273]Banerjee A,Trivedi CM,Damera G,et al.Trichostatin A abrogates airway constriction,but not inflammation,in murine and human asthma models[J].Am J Respir Cell Mol Biol,2012,46:132-138.
[274]Hou X,Wan H,Ai X,et al.Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma[J].Clin Respir J,2016,10:371-379.
[275]Royce SG,Dang W,Yuan G,et al.Effects of the histone deacetylase inhibitor,trichostatin A,in a chronic allergic airways disease model in mice[J].Arch Immunol Ther Exp(Warsz),2012,60:295-306.
[276]Toki S,Goleniewska K,Reiss S,et al.The histone deacetylase inhibitor trichostatin A suppresses murine innate allergic inflammation by blocking group 2 innate lymphoid cell(ILC2)activation[J].Thorax,2016,71:633-645.
[277]Perry MM,Durham AL,Austin PJ,et al.BET bromodomains regulate transforming growth factor-β-induced proliferation and cytokine release in asthmatic airway smooth muscle[J].J Biol Chem,2015,290:9111-9121.
[278]Nozik-Grayck E,Woods C,Stearman RS,et al.Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension[J].Am J Physiol Lung Cell Mol Physiol,2016,311:L124-L134.
[279]Yang S,Banerjee S,Freitas A,et al.mi R-21 regulates chronic hypoxiainduced pulmonary vascular remodeling[J].Am J Physiol Lung Cell Mol Physiol,2012,302:L521-L529.
[280]Williams AE,Larner-Svensson H,Perry MM,et al.Micro RNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy[J].PLo S one,2009,4:e5889.
[281]Kuhn AR,Schlauch K,Lao R,et al.Micro RNA expression in human airway smooth muscle cells:role of mi R-25 in regulation of airway smooth muscle phenotype[J].Am J Respir Cell Mol Biol,2010,42:506-513.
[282]Larner-Svensson HM,Williams AE,Tsitsiou E,et al.Pharmacological studies of the mechanism and function of interleukin-1β-induced mi RNA-146a expression in primary human airway smooth muscle[J].Respir Res,2010,11:68.
[283]Comer BS,Camoretti-Mercado B,Kogut PC,et al.Micro RNA-146a and micro RNA-146b expression and anti-inflammatory function in human airway smooth muscle[J].Am J Physiol Lung Cell Mol Physiol,2014,307:L727-L734.
[284]Jude JA,Dileepan M,Subramanian S,et al.mi R-140-3p regulation of TNF-α-induced CD38 expression in human airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2012,303:L460-L468.
[285]Deshpande DA,Dileepan M,Walseth TF,et al.Micro RNA regulation of airway inflammation and airway smooth muscle function:relevance to asthma[J].Drug Dev Res,2015,76:286-295.
[286]Dileepan M,Jude JA,Rao SP,et al.Micro RNA-708 regulates CD38expression through signaling pathways JNK MAP kinase and PTEN/AKT in human airway smooth muscle cells[J].Respir Res,2014,15:107.
[287]Guedes AG,Deshpande DA,Dileepan M,et al.CD38 and airway hyperresponsiveness:studies on human airway smooth muscle cells and mouse models[J].Can J Physiol Pharmacol,2015,93:145-153.
[288]Mohamed JS,Hajira A,Li Z,et al.Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and micro RNA-26a[J].J Biol Chem,2011,286:43394-43404.
[289]Hu R,Pan W,Fedulov AV,et al.Micro RNA-10a controls airway smooth muscle cell proliferation via direct targeting of the PI3 kinase pathway[J].FASEB J,2014,28:2347-2357.
[290]Chen M,Huang L,Zhang W,et al.Mi R-23b controls TGF-β1 induced airway smooth muscle cell proliferation via TGFβR2/p-Smad3 signals[J].Mol Immunol,2016,70:84-93.
[291]Liu Y,Yang K,Sun X,et al.Mi R-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1[J].Exp Lung Res,2015,41:363-369.
[292]Liu Y,Sun X,Wu Y,et al.Effects of mi RNA-145 on airway smooth muscle cells function[J].Mol Cell Biochem,2015,409:135-143.
[293]Liao G,Panettieri RA,Tang DD.Micro RNA-203 negatively regulates c-Abl,ERK1/2 phosphorylation,and proliferation in smooth muscle cells[J].Physiol Rep,2015,3.
[294]Perry MM,Baker JE,Gibeon DS,et al.Airway smooth muscle hyperproliferation is regulated by micro RNA-221 in severe asthma[J].Am J Respir Cell Mol Biol,2014,50:7-17.
[295]Dileepan M,Jude JA,Rao SP,et al.Micro RNA-708 regulates CD38expression through signaling pathways JNK MAP kinase and PTEN/AKT in human airway smooth muscle cells[J].Respir Res,2014,15:107.
[296]Kuhn AR,Schlauch K,Lao R,et al.Micro RNA expression in human airway smooth muscle cells:role of mi R-25 in regulation of airway smooth muscle phenotype[J].Am J Respir Cell Mol Biol,2010,42:506-513.
[297]Aravamudan B,Thompson MA,Pabelick CM,et al.Mitochondria in lung diseases[J].Expert Rev Respir Med,2013,7:631-646.
[298]Contreras L,Drago I,Zampese E,et al.Mitochondria:the calcium connection[J].Biochim Biophys Acta,2010,1797:607-618.
[299]Rizzuto R,De Stefani D,Raffaello A,et al.Mitochondria as sensors and regulators of calcium signalling[J].Nat Rev Mol Cell Biol,2012,13:566-578.
[300]Aravamudan B,Thompson MA,Pabelick CM,et al.Mitochondria in lung diseases[J].Expert Rev Respir Med,2013,7:631-646.
[301]Girodet Po,Allard B,Thumerel M,et al.Bronchial smooth muscle remodeling in nonsevere asthma[J].Am J Respir Crit Care Med,2016,193:627-633.
[302]Chen T,Zhu L,Wang T,et al.Mitochondria depletion abolishes agonistinduced Ca2+plateau in airway smooth muscle cells:potential role of H2o2[J].Am J Physiol Lung Cell Mol Physiol,2010,298:L178-L188.
[303]Michaeloudes C,Sukkar MB,Khorasani NM,et al.TGF-βregulates Nox4,Mn So D and catalase expression,and IL-6 release in airway smooth muscle cells[J].Am J Physiol Lung Cell Mol Physiol,2011,300:L295-L304.
[304]Aravamudan B,Thompson M,Sieck GC,et al.Functional effects of cigarette smoke-induced changes in airway smooth muscle mitochondrial morphology[J].J Cell Physiol,2017,232(5):1053-1068.
[305]Delmotte P,Sieck GC.Interaction between endoplasmic/sarcoplasmic reticulum stress(ER/SR stress),mitochondrial signaling and Ca2+regulation in airway smooth muscle(ASM)[J].Can J Physiol Pharmacol,2015,93:97-110.
[306]Delmotte P,Yang B,Thompson MA,et al.Inflammation alters regional mitochondrial Ca2+in human airway smooth muscle cells[J].Am J Physiol Cell Physiol,2012,303:C244-C256.
[307]Guo q,Li H,Liu J,et al.Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHo P signaling in a murine model of neutrophilic asthma[J].J Asthma,2017,54(2):125-133.
[308]Hsu KJ,Turvey SE.Functional analysis of the impact of o RMDL3expression on inflammation and activation of the unfolded protein response in human airway epithelial cells[J].Allergy Asthma Clin Immunol,2013,9:4.
[309]Kim SR,Lee YC.Endoplasmic reticulum stress and the related signaling networks in severe asthma[J].Allergy Asthma Immunol Res,2015,7:106-117.
[310]Lee KS,Jeong JS,Kim SR,et al.Phosphoinositide 3-kinase-δregulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress[J].Thorax,2016,71:52-63.
[311]Hoffman SM,Tully JE,Nolin JD,et al.Endoplasmic reticulum stress mediates house dust mite-induced airway epithelial apoptosis and fibrosis[J].Respir Res,2013,14:141.
[312]Makhija L,Krishnan V,Rehman R,et al.Chemical chaperones mitigate experimental asthma by attenuating endoplasmic reticulum stress[J].Am J Respir Cell Mol Biol,2014,50:923-931.
[313]Wang S,Robinet P,Smith JD,et al.o RMDL orosomucoid-like proteins are degraded by free-cholesterol-loading-induced autophagy[J].Proc Natl Acad Sci u SA,2015,112:3728-3733.