TGF-β受体与肝纤维化的研究现状
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摘要
转化生长因子-β(TGF-β)是致肝纤维化的重要细胞因子,其必须与TGF-β受体(TβR)结合才能发挥生物学作用。研究TβR与肝纤维化发生、发展的关系,已成为研究肝纤维化形成机制的热点。本文就近几年TβR与肝纤维化关系的研究进展进行综述。
Transforming growth factor-beta(TGF-β)is a cytokine that causes liver fibrosis.It must be combined with TGF-βreceptor(TβR)to exert its biological effects.Thus,the relationship between TβR and the development of liver fibrosis has been studied,which has become a hotspot for studying the mechanism of liver fibrosis formation.This article reviews the research progress of the relationship between TβR and liver fibrosis in recent years.
Transforming growth factor-beta(TGF-β)is a cytokine that causes liver fibrosis.It must be combined with TGF-βreceptor(TβR)to exert its biological effects.Thus,the relationship between TβR and the development of liver fibrosis has been studied,which has become a hotspot for studying the mechanism of liver fibrosis formation.This article reviews the research progress of the relationship between TβR and liver fibrosis in recent years.
引文
[1]WEISKIRCHEN R,TACKE F.Liver fibrosis:from pathogenesis to novel therapies[J].Digest Dis,2016,34(4):410-422.
[2]FUNG E,TSUKAMOTO H.Morphogen-related therapeutic targets for liver fibrosis[J].Clin Res Hepatol Gastroenterol,2015,39(1):S69-S74.
[3]LI H J,LAN J Q,HAN C S,et al.Brg1promotes liver fibrosis via activation of hepatic stellate cells[J].Exp Cell Res,2018,364(2):191-197.
[4]YANG J W,WOOK K,LiIM S C.The role of Pin1in liver fibrosis:Regulation of Tgf-beta 1 expression and Smad2/3phosphorylation[J].J Hepatol,2014,60(6):1235-1241.
[5]FAN X B,ZHANG QN,LI S,et al.Attenuation of CCl4-Induced hepatic fibrosis in mice by vaccinating against TGF-beta 1[J].PLOS One,2013,8(12):e82190.
[6]CHUNG C L,WANG S W,MARTIN R,et al.Pentachloropseudilin inhibits transforming growth factor-(TGF-)activity by accelerating Cell-Surface TypeⅡTGF-receptor turnover in target cells[J].Chembiochem,2018,19(8):851-864.
[7]GYRFI A H,MATEI A E,DISTLER J H W.Targeting TGF-βsignaling for the treatment of fibrosis[J].Matrix Biol,2018,68(1):8-27.
[8]WALTON K L,JOHNSON K E,HARRISON C A.Targeting TGF-beta mediated SMAD signaling for the prevention of fibrosis[J].Front Pharmacol,2017,8(4):461.
[9]DAVID C J,HUANG Y H,CHEN M,et al.TGF-beta tumor suppression through a lethal EMT[J].Cell,2016,164(5):1015-1030.
[10]YAKYMOVYCH I,YAKYMOVYCH M,ZANG G X,et al.CIN85modulates TGF beta signaling by promoting the presentation of TGF beta receptors on the cell surface[J].J Cell Biol,2015,210(2):319-332.
[11]LIAO X H,ZHANG L,CHEN G T,et al.Augmenter of liver regeneration inhibits TGF-beta 1-induced renal tubular epithelial-to-mesenchymal transition via suppressing T beta RⅡexpression in vitro[J].Exp Cell Res,2014,327(2):287-296.
[12]NAKAJIMA A,ITO Y,TANAKA E,et al.Functional role of TGF-beta receptors during palatal fusion in vitro[J].Arch Oral Biol,2014,59(11):1192-1204.
[13]LUCKETT-CHASTAIN L R,COTTRELL M L,KAWAR BM,et al.Interleukin(IL)-6 modulates transforming growth factor-beta receptorⅠandⅡ(TGF-beta RⅠandⅡ)function in epidermal keratinocytes[J].Exp Dermatol,2017,26(8):697-704.
[14]LA J,REED E,CHAN Lan,et al.Downregulation of TGF-beta receptor-2expression and signaling through inhibition of Na/K-ATPase[J].PLOS One,2016,11(12):e0168363.
[15]POMERANIEC L,HECTOR-GREENE M,EHRLICHM A,et al.Regulation of TGF-beta receptor hetero-oligomerization and signaling by endoglin[J].Mol Biol Cell,2015,26(17):3117-3127.
[16]XU Z J,SHU S,LI Z J,et al.Liuwei dihuang pill treats diabetic nephropathy in rats by inhibiting of TGF-beta/SMADS,MAPK,and NF-kB and upregulating expression of cytoglobin in renal tissues[J].Medicine,2017,96(3):e5879.
[17]JUNG S M,LEE J H,PARK J,et al.Smad6inhibits noncanonical TGF-β1signalling by recruiting the deubiquitinase A20to TRAF6[J].Nat Commun,2013,4:2562.
[18]YAN X H,LIAO H W,CHENG M Z,et al.Smad7protein interacts with receptor-regulated smads(R-Smads)to inhibit transforming growth factor-beta(TGF-beta/Smad signaling[J].J Biol Chem,2016,291(1):382-392.
[19]FABREGAT I,MORENO-CCERES J,SNCHEZ A,et al.TGF-βsignaling and liver disease[J].FEBS J,2016,283(12):2219.
[20]LIN Y C,LUO H Y,WANG X,et al.Flavanones from sedum sarmentosum bunge alleviate CCl4-Induced liver fibrosis in rats by targeting TGF-beta 1/T beta R/Smad Pathway in turn inhibiting epithelial mesenchymal transition[J].EvidenceBased Complementary Alternat Med,2018(8):3080837.
[21]TU X L,ZHANG Y Y,ZHENG X X,et al.TGF-beta-induced hepatocyte lincRNA-p21contributes to liver fibrosis in mice[J].Sci Rep,2017,7(1):2957.
[22]YU Y,DUAN J C,LI Y,et al.Silica nanoparticles induce liver fibrosis via TGF-beta(1)/Smad3pathway in ICRmice[J].Int J Nano Med,2017,12:6045-6057.
[23]ZHOU Y P,TONG X,REN S,et al.Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-beta 1/Smads signaling pathway modulation[J].J Ethnopharmacol,2016,190(1):83-90.
[24]KHALIL A M,DOTIMAS H,KAHN J,et al.Differential binding activity of TGF-beta family proteins to select TGF-beta receptors[J].J Pharmacol Exp Therapeut,2016,358(3):423-430.
[25]HONG-CHUANG M A,BAI H,ZHANG Z,et al.Therapeutically effect of a novel truncated transforming growth factor-βtypeⅡreceptor protein in rat hepatic fibrosis[J].China Biotechnol,2014,8(1):72.
[26]JOVANOVIC B,PICKUP M W,CHYTIL A,et al.T beta RⅢExpression in human breast cancer stroma and the role of soluble T beta RⅢin breast cancer associated fibroblasts[J].Cancers,2016,8(11):100.
[27]ELDERBROOM J L,HUANG J J,GATZA C E,et al.Ectodomain shedding of TβRⅢis required for TβRⅢ-mediated suppression of TGF-βsignaling and breast cancer migration and invasion[J].Mol Biol Cell,2014,25(16):2320-2332.
[28]LI D,XU D Y,LU Z Y,et al.Overexpression of transforming growth factor typeⅢreceptor restores TGF-beta 1sensitivity in human tongue squamous cell carcinoma cells[J].Biosci Rep,2015,35(4):e0024.
[29]TAZAT K,HECTOR-GREENE M,BLOBE G C,et al.TβRⅢindependently binds typeⅠand typeⅡTGF-βreceptors to inhibit TGF-βsignaling[J].Mol Biol Cell,2015,26(19):3535-3545.
[30]ALSAMMAN M,STERZER V,MEURER S K,et al.Endoglin in human liver disease and murine models of liver fibrosis-A protective factor against liver fibrosis[J].Liver Int,2018,38(5):858-867.
[2]FUNG E,TSUKAMOTO H.Morphogen-related therapeutic targets for liver fibrosis[J].Clin Res Hepatol Gastroenterol,2015,39(1):S69-S74.
[3]LI H J,LAN J Q,HAN C S,et al.Brg1promotes liver fibrosis via activation of hepatic stellate cells[J].Exp Cell Res,2018,364(2):191-197.
[4]YANG J W,WOOK K,LiIM S C.The role of Pin1in liver fibrosis:Regulation of Tgf-beta 1 expression and Smad2/3phosphorylation[J].J Hepatol,2014,60(6):1235-1241.
[5]FAN X B,ZHANG QN,LI S,et al.Attenuation of CCl4-Induced hepatic fibrosis in mice by vaccinating against TGF-beta 1[J].PLOS One,2013,8(12):e82190.
[6]CHUNG C L,WANG S W,MARTIN R,et al.Pentachloropseudilin inhibits transforming growth factor-(TGF-)activity by accelerating Cell-Surface TypeⅡTGF-receptor turnover in target cells[J].Chembiochem,2018,19(8):851-864.
[7]GYRFI A H,MATEI A E,DISTLER J H W.Targeting TGF-βsignaling for the treatment of fibrosis[J].Matrix Biol,2018,68(1):8-27.
[8]WALTON K L,JOHNSON K E,HARRISON C A.Targeting TGF-beta mediated SMAD signaling for the prevention of fibrosis[J].Front Pharmacol,2017,8(4):461.
[9]DAVID C J,HUANG Y H,CHEN M,et al.TGF-beta tumor suppression through a lethal EMT[J].Cell,2016,164(5):1015-1030.
[10]YAKYMOVYCH I,YAKYMOVYCH M,ZANG G X,et al.CIN85modulates TGF beta signaling by promoting the presentation of TGF beta receptors on the cell surface[J].J Cell Biol,2015,210(2):319-332.
[11]LIAO X H,ZHANG L,CHEN G T,et al.Augmenter of liver regeneration inhibits TGF-beta 1-induced renal tubular epithelial-to-mesenchymal transition via suppressing T beta RⅡexpression in vitro[J].Exp Cell Res,2014,327(2):287-296.
[12]NAKAJIMA A,ITO Y,TANAKA E,et al.Functional role of TGF-beta receptors during palatal fusion in vitro[J].Arch Oral Biol,2014,59(11):1192-1204.
[13]LUCKETT-CHASTAIN L R,COTTRELL M L,KAWAR BM,et al.Interleukin(IL)-6 modulates transforming growth factor-beta receptorⅠandⅡ(TGF-beta RⅠandⅡ)function in epidermal keratinocytes[J].Exp Dermatol,2017,26(8):697-704.
[14]LA J,REED E,CHAN Lan,et al.Downregulation of TGF-beta receptor-2expression and signaling through inhibition of Na/K-ATPase[J].PLOS One,2016,11(12):e0168363.
[15]POMERANIEC L,HECTOR-GREENE M,EHRLICHM A,et al.Regulation of TGF-beta receptor hetero-oligomerization and signaling by endoglin[J].Mol Biol Cell,2015,26(17):3117-3127.
[16]XU Z J,SHU S,LI Z J,et al.Liuwei dihuang pill treats diabetic nephropathy in rats by inhibiting of TGF-beta/SMADS,MAPK,and NF-kB and upregulating expression of cytoglobin in renal tissues[J].Medicine,2017,96(3):e5879.
[17]JUNG S M,LEE J H,PARK J,et al.Smad6inhibits noncanonical TGF-β1signalling by recruiting the deubiquitinase A20to TRAF6[J].Nat Commun,2013,4:2562.
[18]YAN X H,LIAO H W,CHENG M Z,et al.Smad7protein interacts with receptor-regulated smads(R-Smads)to inhibit transforming growth factor-beta(TGF-beta/Smad signaling[J].J Biol Chem,2016,291(1):382-392.
[19]FABREGAT I,MORENO-CCERES J,SNCHEZ A,et al.TGF-βsignaling and liver disease[J].FEBS J,2016,283(12):2219.
[20]LIN Y C,LUO H Y,WANG X,et al.Flavanones from sedum sarmentosum bunge alleviate CCl4-Induced liver fibrosis in rats by targeting TGF-beta 1/T beta R/Smad Pathway in turn inhibiting epithelial mesenchymal transition[J].EvidenceBased Complementary Alternat Med,2018(8):3080837.
[21]TU X L,ZHANG Y Y,ZHENG X X,et al.TGF-beta-induced hepatocyte lincRNA-p21contributes to liver fibrosis in mice[J].Sci Rep,2017,7(1):2957.
[22]YU Y,DUAN J C,LI Y,et al.Silica nanoparticles induce liver fibrosis via TGF-beta(1)/Smad3pathway in ICRmice[J].Int J Nano Med,2017,12:6045-6057.
[23]ZHOU Y P,TONG X,REN S,et al.Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-beta 1/Smads signaling pathway modulation[J].J Ethnopharmacol,2016,190(1):83-90.
[24]KHALIL A M,DOTIMAS H,KAHN J,et al.Differential binding activity of TGF-beta family proteins to select TGF-beta receptors[J].J Pharmacol Exp Therapeut,2016,358(3):423-430.
[25]HONG-CHUANG M A,BAI H,ZHANG Z,et al.Therapeutically effect of a novel truncated transforming growth factor-βtypeⅡreceptor protein in rat hepatic fibrosis[J].China Biotechnol,2014,8(1):72.
[26]JOVANOVIC B,PICKUP M W,CHYTIL A,et al.T beta RⅢExpression in human breast cancer stroma and the role of soluble T beta RⅢin breast cancer associated fibroblasts[J].Cancers,2016,8(11):100.
[27]ELDERBROOM J L,HUANG J J,GATZA C E,et al.Ectodomain shedding of TβRⅢis required for TβRⅢ-mediated suppression of TGF-βsignaling and breast cancer migration and invasion[J].Mol Biol Cell,2014,25(16):2320-2332.
[28]LI D,XU D Y,LU Z Y,et al.Overexpression of transforming growth factor typeⅢreceptor restores TGF-beta 1sensitivity in human tongue squamous cell carcinoma cells[J].Biosci Rep,2015,35(4):e0024.
[29]TAZAT K,HECTOR-GREENE M,BLOBE G C,et al.TβRⅢindependently binds typeⅠand typeⅡTGF-βreceptors to inhibit TGF-βsignaling[J].Mol Biol Cell,2015,26(19):3535-3545.
[30]ALSAMMAN M,STERZER V,MEURER S K,et al.Endoglin in human liver disease and murine models of liver fibrosis-A protective factor against liver fibrosis[J].Liver Int,2018,38(5):858-867.