银屑病患者Jak/STAT信号传导通路基因表达的研究
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摘要
目的:探讨角质形成细胞Jak/STAT信号传导通路上的STAT1、STAT3、SOCS1、SOCS3 4个相关基因在银屑病发病中的作用。方法:收集10例银屑病患者皮损区和非皮损区组织各一块,用实时荧光定量PCR检测组织角质形成细胞中STAT1、STAT3、SOCS1、SOCS3 mRNA的表达,计算各基因mRNA的相对表达水平,探讨其与银屑病皮损发生的关系。结果:银屑病患者皮损区角质形成细胞STAT1、STAT3、SOCS1、SOCS3基因的mRNA表达水平(△Ct值分别为-1.9±1.6、0.6±1.6、0.1±1.0、-0.6±1.1)较非皮损区(△Ct值分别为1.0±1.6、3.7±1.5、4.2±1.2、3.9±1.3)明显增高(P值均<0.01);银屑病患者中角质形成细胞STAT1、STAT3 mRNA的表达水平分别与SOCS1和SOCS3 mRNA的表达水平呈正相关(r=0.84、0.83,P值均<0.01)。结论:角质形成细胞Jak/STAT信号传导通路相关基因可能与银屑病发病有关,需要进行结构与功能相关性的研究以进一步明确。
Objective: To explore the role of Jak/STAT pathway in RNA expression level in patients with psoriasis.Methods:The expression levels of STAT1,STAT3,SOCS1,SOCS3 genes were valuated in keratinocytes from lesional and non-lesional skin of 10 patients with psoriasis by using real-time quantitative PCR technique.Relationships of the expression levels of STAT1,STAT3,SOCS1,SOCS3 mRNA to the pathogenesis of psoriasis were analyzed.Results:Difference between expression levels of STAT1,STAT3,SOCS1,SOCS3 mRNA in keratinocytes of lesional skin and internal reference standard GAPHDH Ct(△Ct) were-1.9±1.6、0.6±1.6、0.1±1.0、-0.6±1.1 respectively,which were significantly higher than that of non-lesional skin(△Ct were 1.0±1.6,3.7±1.5,4.2±1.2,3.9±1.3) respectively.The expression levels of STAT1,STAT3 mRNA of keratinocytes was found highly correlate to the that of SOCS1,as well as SOCS3 mRNA(r= 0.84、0.83,P<0.01).Conclusion:Jak/STAT pathway is involved in the pathogenesis of psoriasis.Further investigation is required for the understanding of the function of these abnormally expressed genes.
Objective: To explore the role of Jak/STAT pathway in RNA expression level in patients with psoriasis.Methods:The expression levels of STAT1,STAT3,SOCS1,SOCS3 genes were valuated in keratinocytes from lesional and non-lesional skin of 10 patients with psoriasis by using real-time quantitative PCR technique.Relationships of the expression levels of STAT1,STAT3,SOCS1,SOCS3 mRNA to the pathogenesis of psoriasis were analyzed.Results:Difference between expression levels of STAT1,STAT3,SOCS1,SOCS3 mRNA in keratinocytes of lesional skin and internal reference standard GAPHDH Ct(△Ct) were-1.9±1.6、0.6±1.6、0.1±1.0、-0.6±1.1 respectively,which were significantly higher than that of non-lesional skin(△Ct were 1.0±1.6,3.7±1.5,4.2±1.2,3.9±1.3) respectively.The expression levels of STAT1,STAT3 mRNA of keratinocytes was found highly correlate to the that of SOCS1,as well as SOCS3 mRNA(r= 0.84、0.83,P<0.01).Conclusion:Jak/STAT pathway is involved in the pathogenesis of psoriasis.Further investigation is required for the understanding of the function of these abnormally expressed genes.
引文
[1]Nestle FO,Kaplan DH,Barker J.Psoriasis[J].N EnglJ Med,2009,361(5):496-509.
[2]Gudjonsson JE,Elder JT.Psoriasis:epidemiology[J].Clin Dermatol,2007,25(6):535-546.
[3]Lew W,Bowcock AM,Krueger JG.Psoriasis vulgaris:cutaneous lymphoid tissue supports T-cell activation and“Type 1”inflammatory gene expression[J].Trends Im-munol,2004,25(6):295-305.
[4]Ghoreschi K,Mrowietz U,Rocken M.A molecule solvespsoriasis?Systemic therapies for psoriasis inducing inter-leukin 4 and Th2 responses[J].J Mol Med(Berl),2003,81(8):471-480.
[5]Murray PJ.The JAK-STAT signaling pathway:input andoutput integration[J].J Immunol,2007,178(5):2623-2629.
[6]Sprague AH,Khalil RA.Inflammatory cytokines in vas-cular dysfunction and vascular disease[J].BiochemPharmacol,2009,78(6):539-552.
[7]Li WX.Canonical and non-canonical JAK-STAT signa-ling[J].Trends Cell Biol,2008,18(11):545-551.
[8]Lin Q,Lai R,Chirieac LR,et al.Constitutive activationof JAK3/STAT3 in colon carcinoma tumors and celllines:inhibition of JAK3/STAT3 signaling induces apop-tosis and cell cycle arrest of colon carcinoma cells[J].Am J Pathol,2005,167(4):969-980.
[9]Aoki Y,Feldman GM,Tosato G.Inhibition of STAT3signaling induces apoptosis and decreases survivin expres-sion in primary effusion lymphoma[J].Blood,2003,101(4):1535-1542.
[10]Sano S,Chan KS,Carbajal S,et al.Stat3 links activatedkeratinocytes and immunocytes required for developmentof psoriasis in a novel transgenic mouse model[J].NatMed,2005,11(1):43-49.
[11]Palmer DC,Restifo NP.Suppressors of cytokine signa-ling(SOCS)in T cell differentiation,maturation,andfunction[J].Trends Immunol,2009,30(12):592-602.
[12]Croker BA,Kiu H,Nicholson SE.SOCS regulation ofthe JAK/STAT signalling pathway[J].Semin Cell DevBiol,2008,19(4):414-422.
[13]Yoshimura A.Regulation of cytokine signaling by theSOCS and Spred family proteins[J].Keio J Med,2009,58(2):73-83.
[2]Gudjonsson JE,Elder JT.Psoriasis:epidemiology[J].Clin Dermatol,2007,25(6):535-546.
[3]Lew W,Bowcock AM,Krueger JG.Psoriasis vulgaris:cutaneous lymphoid tissue supports T-cell activation and“Type 1”inflammatory gene expression[J].Trends Im-munol,2004,25(6):295-305.
[4]Ghoreschi K,Mrowietz U,Rocken M.A molecule solvespsoriasis?Systemic therapies for psoriasis inducing inter-leukin 4 and Th2 responses[J].J Mol Med(Berl),2003,81(8):471-480.
[5]Murray PJ.The JAK-STAT signaling pathway:input andoutput integration[J].J Immunol,2007,178(5):2623-2629.
[6]Sprague AH,Khalil RA.Inflammatory cytokines in vas-cular dysfunction and vascular disease[J].BiochemPharmacol,2009,78(6):539-552.
[7]Li WX.Canonical and non-canonical JAK-STAT signa-ling[J].Trends Cell Biol,2008,18(11):545-551.
[8]Lin Q,Lai R,Chirieac LR,et al.Constitutive activationof JAK3/STAT3 in colon carcinoma tumors and celllines:inhibition of JAK3/STAT3 signaling induces apop-tosis and cell cycle arrest of colon carcinoma cells[J].Am J Pathol,2005,167(4):969-980.
[9]Aoki Y,Feldman GM,Tosato G.Inhibition of STAT3signaling induces apoptosis and decreases survivin expres-sion in primary effusion lymphoma[J].Blood,2003,101(4):1535-1542.
[10]Sano S,Chan KS,Carbajal S,et al.Stat3 links activatedkeratinocytes and immunocytes required for developmentof psoriasis in a novel transgenic mouse model[J].NatMed,2005,11(1):43-49.
[11]Palmer DC,Restifo NP.Suppressors of cytokine signa-ling(SOCS)in T cell differentiation,maturation,andfunction[J].Trends Immunol,2009,30(12):592-602.
[12]Croker BA,Kiu H,Nicholson SE.SOCS regulation ofthe JAK/STAT signalling pathway[J].Semin Cell DevBiol,2008,19(4):414-422.
[13]Yoshimura A.Regulation of cytokine signaling by theSOCS and Spred family proteins[J].Keio J Med,2009,58(2):73-83.