IRF3调控瘢痕疙瘩成纤维细胞增殖和细胞外基质表达的研究  

IRF3 regulates proliferation of fibroblasts and expression of extracellular matrix proteins in keloid

作　　者：张谊[1] 洪炜龙[2] 徐云升[1] 李智铭[1] 张璃[1] 林孝华[1] 张启瑜[3] ZHANG Yi;XU Yunsheng;HONG Weilong(Department of Dermatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China)

机构地区：[1]温州医科大学第一附属医院皮肤科,325000 [2]温州医科大学第一附属医院外科实验室,325000 [3]温州医科大学第一附属医院肝胆外科,325000

出　　处：《浙江医学》2018年第5期433-438,共6页Zhejiang Medical Journal

基　　金：浙江省医药卫生一般研究计划项目(2015KYB244);浙江省教育厅高教重中之重学科(2008-255)

摘　　要：目的通过观察干扰素调节因子3(IRF3)对瘢痕疙瘩成纤维细胞增殖和细胞外基质表达的作用,探讨IRF3在皮肤纤维化中的调控机制。方法取行瘢痕疙瘩切除手术的10例患者的术中切除的瘢痕疙瘩组织为研究材料,另择8例外科手术患者的正常皮肤组织为对照,培养两者的成纤维细胞。采用real-time RT-PCR、Western blot检测成纤维细胞IRF3 mRNA、蛋白表达水平,转染siRNAs-IRF3后IRF3蛋白水平;检测TGF-β1诱导后瘢痕疙瘩成纤维细胞增殖情况,细胞外基质Ⅰ型胶原蛋白(collagenⅠ)、a-平滑肌肌动蛋白(a-SMA)I型胶原与TGF-β受体Ⅰ、Ⅱ,及TGF-β1信号通路调节蛋白p-Smad2、Smad2、p-Smad3、Smad3表达水平。结果 IRF3在瘢痕疙瘩组织中表达显著上调。下调IRF3的表达,显著抑制瘢痕疙瘩成纤维细胞的增殖,并抑制collagenⅠ、a-SMA的表达,同时抑制TGF-β1诱导的瘢痕疙瘩成纤维细胞的TGF-β受体Ⅰ、Ⅱ的表达。下调IRF3的表达亦抑制瘢痕疙瘩成纤维细胞p-Smad2、Smad2、p-Smad3、Smad3表达水平。结论 IRF3表达下调通过抑制TGF-β1/Smad信号通路,抑制瘢痕疙瘩成纤维细胞增殖和细胞外基质的表达。IRF3或为治疗瘢痕疙瘩新的靶点。Objective To investigate the expression of Interferon regulatory factor3(IRF3)in keloid,and its function in regulating proliferation of keloid-derived fibroblasts(KFs)and expression of extracellular matrix(ECM)proteins.Methods Ten tissue samples of keloid and8samples of normal skin were cultured and fibroblasts were isolated.The expression of IRF3mRNA and protein in human keloid tissues were detected by qRT-PCR and Western blotting,respectively.KFs were incubated with siRNAs-IRF3or scramble for48h;then cells were treated with TGF-β1(10ng/ml)for24h.KFs proliferation,the expression of type I collagen,a-SMA,TGF-βRI/II,p-Smad2,Smad2,p-Smad3and Smad3proteins were detected.Results Expression of IRF3mRNA and proterin was significantly higher in human keloid tissues than that in normal skin tissues.Down-regulation of IRF3significantly inhibited KF proliferation and the expression of type I collagen,a-SMA,TGF-βreceptor I and II in TGF-β1-stimulated KFs.Furthermore,down-regulation of IRF3suppressed the phosphorylation levels of Smad2and Smad3in human KFs induced by TGF-β1.Conclusion Down-regulation of IRF3inhibits the proliferation and ECM expression in KFs via suppressing the TGF-β1/Smad signaling pathway.IRF3may represent a novel target for treatment of the keloid disease.

关 键 词：干扰素调节因子3 瘢痕疙瘩成纤维细胞 细胞外基质 TGF-Β1/SMAD 通路 

分 类 号：R751[医药卫生—皮肤病学与性病学]