银屑病的发病机制及其研究进展
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摘要
银屑病是一种慢性炎症性皮肤病,其发生发展与免疫功能失调、血管损伤、信号转导通路紊乱及银屑病相关基因表达失衡密切相关。近年来,银屑病发病机制的研究取得了较大进展。银屑病患者血清中的辅助性T细胞17及其细胞因子明显增多,血管内皮生长因子水平降低可以改善银屑病皮损组织的病变,角质形成细胞内的信号转导通路异常与角质形成细胞的异常增殖显著相关。此外,银屑病患者细胞内的致病基因表达,以及差异性微RNAs表达水平异常也与皮损区病变程度密切相关。这些新进展不仅为进一步阐明银屑病的发病机制提供了实验基础,还为其靶向治疗提供了新方向。
Psoriasis is a chronic inflammatory skin disease. Its occurrence and development are closely related to immune dysfunction,vascular injury,disturbance of signal transduction pathway and imbalance of psoriasis-related gene expression. In recent years,great progress has been made in the research of pathogenesis of psoriasis. Serum T helper cell 17 and its cytokines significantly increase in patients with psoriasis. Reduced levels of vascular endothelial growth factor can improve lesions in psoriatic lesions. Abnormal signal transduction pathways in keratinocytes are significantly correlated with abnormal proliferation of keratinocytes. In addition,intracellular expression of pathogenic genes and abnormal expression of differentially expressed microRNAs in psoriasis patients are also closely related to in the severity of the lesions. These new advances not only provide an experimental basis for further elucidating the pathogenesis of psoriasis,but also provide a new direction for the targeted therapy.
Psoriasis is a chronic inflammatory skin disease. Its occurrence and development are closely related to immune dysfunction,vascular injury,disturbance of signal transduction pathway and imbalance of psoriasis-related gene expression. In recent years,great progress has been made in the research of pathogenesis of psoriasis. Serum T helper cell 17 and its cytokines significantly increase in patients with psoriasis. Reduced levels of vascular endothelial growth factor can improve lesions in psoriatic lesions. Abnormal signal transduction pathways in keratinocytes are significantly correlated with abnormal proliferation of keratinocytes. In addition,intracellular expression of pathogenic genes and abnormal expression of differentially expressed microRNAs in psoriasis patients are also closely related to in the severity of the lesions. These new advances not only provide an experimental basis for further elucidating the pathogenesis of psoriasis,but also provide a new direction for the targeted therapy.
引文
[1] Di Meglio P,Villanova F,Nestle FO. Psoriasis[J]. Cold Spring Harb Perspect Med,2014,4(8). pii:a015354.
[2] Krueger JG,Bowcock A. Psoriasis pathophysiology:Current concepts of pathogenesis[J]. Ann Rheum Dis,2005,64 Suppl 2:ii30-36.
[3] Ruano J,Suárez-Fari1as M,Shemer A,et al. Molecular and cellular profiling of scalp psoriasis reveals differences and similarities compared to skin psoriasis[J]. PLo S One,2016,11(2):e0148450.
[4] Padovan E. Modulation of CD+4T helper cell memory responses in the human skin[J]. Int Arch Allergy Immunol,2017,173(3):121-137.
[5] Casciano F,Pigatto PD,Secchiero P,et al. T cell hierarchy in the pathogenesis of psoriasis and associated cardiovascular comorbidities[J]. Front Immunol,2018,9:1390.
[6] Yousefzadeh H,Jabbari Azad F,Rastin M,et al. Expression of Th1 and Th2 cytokine and associated transcription factors in peripheral blood mononuclear cells and correlation with disease severity[J]. Rep Biochem Mol Biol,2017,6(1):102-111.
[7] Diani M,Altomare G,Reali E. T helper cell subsets in clinical manifestations of psoriasis[J]. J Immunol Res,2016,2016:7692024.
[8] Boniface K,Jacquemin C,Darrigade AS,et al. Vitiligo skin is imprinted with resident memory CD8T cells expressing CXCR3[J].J Invest Dermatol,2018,138(2):355-364.
[9] Kagami S,Rizzo HL,Lee JJ,et al. Circulating Th17,Th22,and Th1 cells are increased in psoriasis[J]. J Invest Dermatol,2010,130(5):1373-1383.
[10] van der Fits L,Mourits S,Voerman JS,et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis[J]. J Immunol,2009,182(9):5836-5845.
[11] Sbidian E,Chaimani A,Garcia-Doval I,et al. Systemic pharmacological treatments for chronic plaque psoriasis:A network metaanalysis[J/CD]. Cochrane Database Syst Rev,2017,12:CD011535.
[12] Molinelli E,Campanati A,Ganzetti G,et al. Biologic therapy in psoriasis(PartⅡ):Efficacy and safety of new treatment targeting IL23/IL-17 pathways[J]. Curr Pharm Biotechnol,2017,18(12):964-978.
[13] Johnson-Huang LM,Suárez-Fari1as M,Sullivan-Whalen M,et al.Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques[J]. J Invest Dermatol,2010,130(11):2654-2663.
[14] Bojko A,Ostasz R,Biaecka M,et al. IL12B,IL23A,IL23R and HLA-C*06 genetic variants in psoriasis susceptibility and response to treatment[J]. Hum Immunol,2018,79(4):213-217.
[15] Foerster J,Boswell K,West J,et al. Narrowband UVB treatment is highly effective and causes a strong reduction in the use of steroid and other creams in psoriasis patients in clinical practice[J].PLo S One,2017,12(8):e0181813.
[16] Ma L,Xue HB,Guan XH,et al. Possible pathogenic role of T helper type 9 cells and interleukin(IL)-9 in atopic dermatitis[J]. Clin Exp Immunol,2014,175(1):25-31.
[17] Singh TP,Sch9n MP,Wallbrecht K,et al. Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis[J].PLo S One,2013,8(1):e51752.
[18] Chowdhury K,Kumar U,Das S,et al. Synovial IL-9 facilitates neutrophil survival,function and differentiation of Th17 cells in rheumatoid arthritis[J]. Arthritis Res Ther,2018,20(1):18.
[19] Owczarczyk-Saczonek A,Czerwińska J,Placek W. The role of regulatory T cells and anti-inflammatory cytokines in psoriasis[J].Acta Dermatovenerol Alp Pannonica Adriat,2018,27(1):17-23.
[20] Nedoszytko B,Lange M,Sokoowska-Wojdyo M,et al. The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases.PartⅠ:Treg properties and functions[J]. Postepy Dermatol Alergol,2017,34(4):285-294.
[21] El-Darouti MA,Hegazy RA,Abdel HRM,et al. Study of T helper(17)and T regulatory cells in psoriatic patients receiving live attenuated varicella vaccine therapy in a randomized controlled trial[J]. Eur J Dermatol,2014,24(4):464-469.
[22] Kichina JV,Goc A,Al-Husein B,et al. PAK1 as a therapeutic target[J]. Expert Opin Ther Targets,2010,14(7):703-725.
[23] Jiang M,Li B,Zhang J,et al. Vascular endothelial growth factor driving aberrant keratin expression pattern contributes to the pathogenesis of psoriasis[J]. Exp Cell Res,2017,360(2):310-319.
[24] Xia YP,Li B,Hylton D,et al. Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis[J]. Blood,2003,102(1):161-168.
[25] Sudhesan A,Rajappa M,Chandrashekar L,et al. Vascular endothelial growth factor(VEGF)gene polymorphisms(rs699947,rs833061,and rs2010963)and psoriatic risk in South Indian Tamils[J]. Hum Immunol,2017,78(10):657-663.
[26] Chen T,Zhang LW,Fu LX,et al. Systemic ALA-PDT effectively blocks the development of psoriasis-like lesions and alleviates leucocyte infiltration in the K14-VEGF transgenic mouse[J]. Clin Exp Dermatol,2017,42(8):849-856.
[27] Liu JH,Wu HH,Zhao YK,et al. Thalidomide improves psoriasislike lesions and inhibits cutaneous VEGF expression without alteration of microvessel density in imiquimod-induced psoriatic mouse model[J]. Curr Vasc Pharmacol,2018,16(5):510-521.
[28] Orecchia V,Regis G,Tassone B,et al. Constitutive STAT3 activation in epidermal keratinocytes enhances cell clonogenicity and favours spontaneous immortalization by opposing differentiation and senescence checkpoints[J]. Exp Dermatol,2015,24(1):29-34.
[29] Kim BH,Na KM,Oh I,et al. Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways[J]. Biochem Pharmacol,2013,85(8):1134-1144.
[30] Galluzzo M,D'Adamio S,Servoli S,et al. Tofacitinib for the treatment of psoriasis[J]. Expert Opin Pharmacother,2016,17(10):1421-1433.
[31] Nada HR,El SDA,Elmasry MF,et al. Expression of Janus Kinase 1in vitiligo&psoriasis before and after narrow band UVB:A casecontrol study[J]. Arch Dermatol Res,2018,310(1):39-46.
[32] Dimitriou ID,Clemenza L,Scotter AJ,et al. Putting out the fire:Coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins[J]. Immunol Rev,2008,224:265-283.
[33] Zhang W,Yi X,An Y,et al. MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes:Implication for the pathogenesis of psoriasis[J]. Cell Death Dis,2018,9(5):567.
[34] Madonna S,Scarponi C,Pallotta S,et al. Anti-apoptotic effects of suppressor of cytokine signaling 3 and 1 in psoriasis[J]. Cell Death Dis,2012,3:e334.
[35] Ahmed CM,Larkin J 3rd,Johnson HM. SOCS1 mimetics and antagonists:A complementary approach to positive and negative regulation of immune function[J]. Front Immunol,2015,6:183.
[36] Kubo M. Therapeutic hope for psoriasis offered by SOCS(suppressor of cytokine signaling)mimetic peptide[J]. Eur J Immunol,2013,43(7):1702-1705.
[37] Liang Y,Xu WD,Peng H,et al. SOCS signaling in autoimmune diseases:Molecular mechanisms and therapeutic implications[J].Eur J Immunol,2014,44(5):1265-1275.
[38] Akiyama T,Carstens E. Neural processing of itch[J]. Neuroscience,2013,250:697-714.
[39] Brederson JD,Kym PR,Szallasi A. Targeting TRP channels for pain relief[J]. Eur J Pharmacol,2013,716(1/3):61-76.
[40] Nilius B,Owsianik G. Transient receptor potential channelopathies[J]. Pflugers Arch,2010,460(2):437-450.
[41] Boesmans W,Owsianik G,Tack J,et al. TRP channels in neurogastroenterology:Opportunities for therapeutic intervention[J].Br J Pharmacol,2011,162(1):18-37.
[42] Cubillos S,Norgauer J. Low vitamin D-modulated calcium-regulating proteins in psoriasis vulgaris plaques:S100A7 overexpression depends on joint involvement[J]. Int J Mol Med,2016,38(4):1083-1092.
[43] BodóE,BíróT,Telek A,et al. A hot new twist to hair biology:Involvement of vanilloid receptor-1(VR1/TRPV1)signaling in human hair growth control[J]. Am J Pathol,2005,166(4):985-998.
[44] Leuner K,Kraus M,Woelfle U,et al. Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation[J]. PLo S One,2011,6(2):e14716.
[45] Huang KF,Ma KH,Liu PS,et al. Baicalein increases keratin 1and 10 expression in Ha CaT keratinocytes via TRPV4 receptor activation[J]. Exp Dermatol,2016,25(8):623-629.
[46]李梅娇,王鹏,蔡敏,等.海南省银屑病患病情况及危险因素流行病学调查[J].中华皮肤科杂志,2013,46(3):157-159.
[47] Israel L,Mellett M. Clinical and Genetic Heterogeneity of CARD14 Mutations in Psoriatic Skin Disease[J]. Front Immunol,2018,9:2239.
[48]李仲桃,汪盛.四川地区汉族单纯性泛发性脓疱型银屑病患者IL36RN基因多态性研究[J].四川大学学报(医学版),2018,49(4):582-586.
[49]张学军.全基因组关联分析对银屑病遗传学研究的启示[J].浙江大学学报(医学版),2009,38(4):333-337.
[50] Patrick MT,Stuart PE,Raja K,et al. Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients[J]. Nat Commun,2018,9(1):4178.
[51] Loft ND,Skov L,Rasmussen MK,et al. Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis[J]. PLo S One,2018,13(2):e0192010.
[52] Zhang XJ,Huang W,Yang S,et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21[J]. Nat Genet,2009,41(2):205-210.
[53] Austin HR,Hoss E,Batie SF,et al. Regulation of late cornified envelope genes relevant to psoriasis risk by plant-derived cyanidin[J]. Biochem Biophys Res Commun,2014,443(4):1275-1279.
[54] Niehues H,Tsoi LC,van der Krieken DA,et al. Psoriasis-associated late cornified envelope(LCE)proteins have antibacterial activity[J].J Invest Dermatol,2017,137(11):2380-2388.
[55] Zhang P,Su Y,Chen H,et al. Abnormal DNA methylation in skin lesions and PBMCs of patients with psoriasis vulgaris[J]. J Dermatol Sci,2010,60(1):40-42.
[56] Zhang P,Zhao M,Liang G,et al. Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris[J]. J Autoimmun,2013,41:17-24.
[57] Gza ewska EK,Niczyporuk M,Lawicki S,et al. Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3,MMP-9 and TIMP-3 in psoriatic patients[J]. Ther Clin Risk Manag,2017,13:575-582.
[58] Sonkoly E,Sthle M,Pivarcsi A. MicroRNAs:Novel regulators in skin inflammation[J]. Clin Exp Dermatol,2008,33(3):312-315.
[59] Chowdhari S,Sardana K,Saini N. miR-4516,a microRNA downregulated in psoriasis inhibits keratinocyte motility by targeting fibronectin/integrinα9 signaling[J]. Biochim Biophys Acta,2017,1863(12):3142-3152.
[60] Hermann H,Runnel T,Aab A,et al. miR-146b probably assists miRNA-146a in the suppression of keratinocyte proliferation and inflammatory responses in psoriasis[J]. J Invest Dermatol,2017,137(9):1945-1954.
[2] Krueger JG,Bowcock A. Psoriasis pathophysiology:Current concepts of pathogenesis[J]. Ann Rheum Dis,2005,64 Suppl 2:ii30-36.
[3] Ruano J,Suárez-Fari1as M,Shemer A,et al. Molecular and cellular profiling of scalp psoriasis reveals differences and similarities compared to skin psoriasis[J]. PLo S One,2016,11(2):e0148450.
[4] Padovan E. Modulation of CD+4T helper cell memory responses in the human skin[J]. Int Arch Allergy Immunol,2017,173(3):121-137.
[5] Casciano F,Pigatto PD,Secchiero P,et al. T cell hierarchy in the pathogenesis of psoriasis and associated cardiovascular comorbidities[J]. Front Immunol,2018,9:1390.
[6] Yousefzadeh H,Jabbari Azad F,Rastin M,et al. Expression of Th1 and Th2 cytokine and associated transcription factors in peripheral blood mononuclear cells and correlation with disease severity[J]. Rep Biochem Mol Biol,2017,6(1):102-111.
[7] Diani M,Altomare G,Reali E. T helper cell subsets in clinical manifestations of psoriasis[J]. J Immunol Res,2016,2016:7692024.
[8] Boniface K,Jacquemin C,Darrigade AS,et al. Vitiligo skin is imprinted with resident memory CD8T cells expressing CXCR3[J].J Invest Dermatol,2018,138(2):355-364.
[9] Kagami S,Rizzo HL,Lee JJ,et al. Circulating Th17,Th22,and Th1 cells are increased in psoriasis[J]. J Invest Dermatol,2010,130(5):1373-1383.
[10] van der Fits L,Mourits S,Voerman JS,et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis[J]. J Immunol,2009,182(9):5836-5845.
[11] Sbidian E,Chaimani A,Garcia-Doval I,et al. Systemic pharmacological treatments for chronic plaque psoriasis:A network metaanalysis[J/CD]. Cochrane Database Syst Rev,2017,12:CD011535.
[12] Molinelli E,Campanati A,Ganzetti G,et al. Biologic therapy in psoriasis(PartⅡ):Efficacy and safety of new treatment targeting IL23/IL-17 pathways[J]. Curr Pharm Biotechnol,2017,18(12):964-978.
[13] Johnson-Huang LM,Suárez-Fari1as M,Sullivan-Whalen M,et al.Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques[J]. J Invest Dermatol,2010,130(11):2654-2663.
[14] Bojko A,Ostasz R,Biaecka M,et al. IL12B,IL23A,IL23R and HLA-C*06 genetic variants in psoriasis susceptibility and response to treatment[J]. Hum Immunol,2018,79(4):213-217.
[15] Foerster J,Boswell K,West J,et al. Narrowband UVB treatment is highly effective and causes a strong reduction in the use of steroid and other creams in psoriasis patients in clinical practice[J].PLo S One,2017,12(8):e0181813.
[16] Ma L,Xue HB,Guan XH,et al. Possible pathogenic role of T helper type 9 cells and interleukin(IL)-9 in atopic dermatitis[J]. Clin Exp Immunol,2014,175(1):25-31.
[17] Singh TP,Sch9n MP,Wallbrecht K,et al. Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis[J].PLo S One,2013,8(1):e51752.
[18] Chowdhury K,Kumar U,Das S,et al. Synovial IL-9 facilitates neutrophil survival,function and differentiation of Th17 cells in rheumatoid arthritis[J]. Arthritis Res Ther,2018,20(1):18.
[19] Owczarczyk-Saczonek A,Czerwińska J,Placek W. The role of regulatory T cells and anti-inflammatory cytokines in psoriasis[J].Acta Dermatovenerol Alp Pannonica Adriat,2018,27(1):17-23.
[20] Nedoszytko B,Lange M,Sokoowska-Wojdyo M,et al. The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases.PartⅠ:Treg properties and functions[J]. Postepy Dermatol Alergol,2017,34(4):285-294.
[21] El-Darouti MA,Hegazy RA,Abdel HRM,et al. Study of T helper(17)and T regulatory cells in psoriatic patients receiving live attenuated varicella vaccine therapy in a randomized controlled trial[J]. Eur J Dermatol,2014,24(4):464-469.
[22] Kichina JV,Goc A,Al-Husein B,et al. PAK1 as a therapeutic target[J]. Expert Opin Ther Targets,2010,14(7):703-725.
[23] Jiang M,Li B,Zhang J,et al. Vascular endothelial growth factor driving aberrant keratin expression pattern contributes to the pathogenesis of psoriasis[J]. Exp Cell Res,2017,360(2):310-319.
[24] Xia YP,Li B,Hylton D,et al. Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis[J]. Blood,2003,102(1):161-168.
[25] Sudhesan A,Rajappa M,Chandrashekar L,et al. Vascular endothelial growth factor(VEGF)gene polymorphisms(rs699947,rs833061,and rs2010963)and psoriatic risk in South Indian Tamils[J]. Hum Immunol,2017,78(10):657-663.
[26] Chen T,Zhang LW,Fu LX,et al. Systemic ALA-PDT effectively blocks the development of psoriasis-like lesions and alleviates leucocyte infiltration in the K14-VEGF transgenic mouse[J]. Clin Exp Dermatol,2017,42(8):849-856.
[27] Liu JH,Wu HH,Zhao YK,et al. Thalidomide improves psoriasislike lesions and inhibits cutaneous VEGF expression without alteration of microvessel density in imiquimod-induced psoriatic mouse model[J]. Curr Vasc Pharmacol,2018,16(5):510-521.
[28] Orecchia V,Regis G,Tassone B,et al. Constitutive STAT3 activation in epidermal keratinocytes enhances cell clonogenicity and favours spontaneous immortalization by opposing differentiation and senescence checkpoints[J]. Exp Dermatol,2015,24(1):29-34.
[29] Kim BH,Na KM,Oh I,et al. Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways[J]. Biochem Pharmacol,2013,85(8):1134-1144.
[30] Galluzzo M,D'Adamio S,Servoli S,et al. Tofacitinib for the treatment of psoriasis[J]. Expert Opin Pharmacother,2016,17(10):1421-1433.
[31] Nada HR,El SDA,Elmasry MF,et al. Expression of Janus Kinase 1in vitiligo&psoriasis before and after narrow band UVB:A casecontrol study[J]. Arch Dermatol Res,2018,310(1):39-46.
[32] Dimitriou ID,Clemenza L,Scotter AJ,et al. Putting out the fire:Coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins[J]. Immunol Rev,2008,224:265-283.
[33] Zhang W,Yi X,An Y,et al. MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes:Implication for the pathogenesis of psoriasis[J]. Cell Death Dis,2018,9(5):567.
[34] Madonna S,Scarponi C,Pallotta S,et al. Anti-apoptotic effects of suppressor of cytokine signaling 3 and 1 in psoriasis[J]. Cell Death Dis,2012,3:e334.
[35] Ahmed CM,Larkin J 3rd,Johnson HM. SOCS1 mimetics and antagonists:A complementary approach to positive and negative regulation of immune function[J]. Front Immunol,2015,6:183.
[36] Kubo M. Therapeutic hope for psoriasis offered by SOCS(suppressor of cytokine signaling)mimetic peptide[J]. Eur J Immunol,2013,43(7):1702-1705.
[37] Liang Y,Xu WD,Peng H,et al. SOCS signaling in autoimmune diseases:Molecular mechanisms and therapeutic implications[J].Eur J Immunol,2014,44(5):1265-1275.
[38] Akiyama T,Carstens E. Neural processing of itch[J]. Neuroscience,2013,250:697-714.
[39] Brederson JD,Kym PR,Szallasi A. Targeting TRP channels for pain relief[J]. Eur J Pharmacol,2013,716(1/3):61-76.
[40] Nilius B,Owsianik G. Transient receptor potential channelopathies[J]. Pflugers Arch,2010,460(2):437-450.
[41] Boesmans W,Owsianik G,Tack J,et al. TRP channels in neurogastroenterology:Opportunities for therapeutic intervention[J].Br J Pharmacol,2011,162(1):18-37.
[42] Cubillos S,Norgauer J. Low vitamin D-modulated calcium-regulating proteins in psoriasis vulgaris plaques:S100A7 overexpression depends on joint involvement[J]. Int J Mol Med,2016,38(4):1083-1092.
[43] BodóE,BíróT,Telek A,et al. A hot new twist to hair biology:Involvement of vanilloid receptor-1(VR1/TRPV1)signaling in human hair growth control[J]. Am J Pathol,2005,166(4):985-998.
[44] Leuner K,Kraus M,Woelfle U,et al. Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation[J]. PLo S One,2011,6(2):e14716.
[45] Huang KF,Ma KH,Liu PS,et al. Baicalein increases keratin 1and 10 expression in Ha CaT keratinocytes via TRPV4 receptor activation[J]. Exp Dermatol,2016,25(8):623-629.
[46]李梅娇,王鹏,蔡敏,等.海南省银屑病患病情况及危险因素流行病学调查[J].中华皮肤科杂志,2013,46(3):157-159.
[47] Israel L,Mellett M. Clinical and Genetic Heterogeneity of CARD14 Mutations in Psoriatic Skin Disease[J]. Front Immunol,2018,9:2239.
[48]李仲桃,汪盛.四川地区汉族单纯性泛发性脓疱型银屑病患者IL36RN基因多态性研究[J].四川大学学报(医学版),2018,49(4):582-586.
[49]张学军.全基因组关联分析对银屑病遗传学研究的启示[J].浙江大学学报(医学版),2009,38(4):333-337.
[50] Patrick MT,Stuart PE,Raja K,et al. Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients[J]. Nat Commun,2018,9(1):4178.
[51] Loft ND,Skov L,Rasmussen MK,et al. Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis[J]. PLo S One,2018,13(2):e0192010.
[52] Zhang XJ,Huang W,Yang S,et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21[J]. Nat Genet,2009,41(2):205-210.
[53] Austin HR,Hoss E,Batie SF,et al. Regulation of late cornified envelope genes relevant to psoriasis risk by plant-derived cyanidin[J]. Biochem Biophys Res Commun,2014,443(4):1275-1279.
[54] Niehues H,Tsoi LC,van der Krieken DA,et al. Psoriasis-associated late cornified envelope(LCE)proteins have antibacterial activity[J].J Invest Dermatol,2017,137(11):2380-2388.
[55] Zhang P,Su Y,Chen H,et al. Abnormal DNA methylation in skin lesions and PBMCs of patients with psoriasis vulgaris[J]. J Dermatol Sci,2010,60(1):40-42.
[56] Zhang P,Zhao M,Liang G,et al. Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris[J]. J Autoimmun,2013,41:17-24.
[57] Gza ewska EK,Niczyporuk M,Lawicki S,et al. Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3,MMP-9 and TIMP-3 in psoriatic patients[J]. Ther Clin Risk Manag,2017,13:575-582.
[58] Sonkoly E,Sthle M,Pivarcsi A. MicroRNAs:Novel regulators in skin inflammation[J]. Clin Exp Dermatol,2008,33(3):312-315.
[59] Chowdhari S,Sardana K,Saini N. miR-4516,a microRNA downregulated in psoriasis inhibits keratinocyte motility by targeting fibronectin/integrinα9 signaling[J]. Biochim Biophys Acta,2017,1863(12):3142-3152.
[60] Hermann H,Runnel T,Aab A,et al. miR-146b probably assists miRNA-146a in the suppression of keratinocyte proliferation and inflammatory responses in psoriasis[J]. J Invest Dermatol,2017,137(9):1945-1954.