RhoA/ROCK-I信号通路与增生性瘢痕成纤维细胞结缔组织生长因子的表达  

RhoA/ROCK-I signaling pathway and expression of connective tissue growth factor in hypertrophic scar fibroblasts

作　　者：戴丽冰[1,2,3] 潘姝[1,2,3] 沈雁[1,2,3] 黄粤[1,2,3] 梁蓉[1,2,3] 康宁[1,2,3] 李叶扬[1,2,3] 李孝建[1,2,3] 谢有富[1,2,3] 李罡[1,2,3] 张琰[1,2,3] 

机构地区：[1]暨南大学医学院第四附属医院 [2]广州市红十字会医院 [3]广州市创伤外科研究所,广东省广州市510220

出　　处：《中国组织工程研究与临床康复》2010年第28期5186-5190,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：广东省中医药局科研项目(No:2007401);广州市中医药;中西医结合科研项目(No:2007A16);广州市科技局项目(No:2008J1-C121);广东省自然科学基金(No:9152800001000009);广州市医药卫生科技重点项目(No:2005-Zdi-03;2006-Zdi-08;2008-Zdi-08;2009-Zdi-05;2009-Zdi-12)~~

摘　　要：背景:前期实验表明增生性瘢痕中RhoA和ROCK-I基因表达较正常皮肤高,提示RhoA/ROCK-I信号通路可能参与了增生性瘢痕的发生,但其在病理性瘢痕中的作用尚不清楚。目的:研究RhoA/ROCK-I信号通路在增生性瘢痕成纤维细胞结缔组织生长因子(connective tissue growth factor,CTGF)表达调控中的作用。方法:分离培养人增生性瘢痕组织来源的成纤维细胞,应用转化生长因子β1及Rho激酶的特异抑制剂Y-27632对细胞进行干预实验。采用实时荧光定量PCR及免疫荧光细胞化学方法检测瘢痕成纤维细胞中RhoA,ROCK-I及CTGF mRNA与蛋白的表达。结果与结论:给予转化生长因子β1后,增生性瘢痕成纤维细胞中RhoA,ROCK-I及CTGF mRNA与蛋白表达明显增多(P<0.01);而Y-27632能阻碍转化生长因子β1的作用;但单独给予Y-27632并不引起瘢痕成纤维细胞中RhoA,ROCK-I及CTGF的mRNA与蛋白表达改变。说明转化生长因子β1可通过RhoA/ROCK-I信号通路调控CTGF mRNA与蛋白的表达,即RhoA/ROCK-I信号通路参与了瘢痕成纤维细胞CTGF的表达调控,阻断RhoA下游通路是增生性瘢痕治疗靶点之一。BACKGROUND： Our previous research has demonstrated that the expression of RhoA and ROCK-I in hypertrophic scar fibroblasts were greater than those in normal skins. These result suggested that RhoA/ROCK signaling pathway might take part in the hypertrophic scar formation. But these effects are still unclear in the hypertrophic scar formation. OBJECTIVE： To study the effects of on expression of connective tissue growth factor （CTGF） in hypertrophic scar fibroblasts. METHODS： Fibroblasts were obtained from human hypertrophic scars and cultured in the mediums. Transforming growth factor β1 （TGF-β1） and Y-27632 were used to intervene the cells. Fluorescent quantitative PCR assay and immunofluorescence cytochemistry were used to quantify the expression and secretion of RhocA, ROCK-I and CTGF in the hypertrophic scar fibroblasts. RESULTS AND CONCLUSION： Upon TGF-β1 treatment, the expression and secretion of RhocA, ROCK-I and CTGF in the hypertrophic scar fibroblasts were significantly increased （P〈0.01）. But these effects of TGF-β1 on ROCK-I and CTGF were inhibited in the TGF-β1＋Y-27632 group. However, there were no expression changes after single Y-27632 treatment. This indicated that TGF-β1 can regulate the expression of CTGF via RhoA/ROCK-I signaling pathway, namely, RhoA/ROCK-I signaling pathway participate the expression regulation of CTGF in hypertrophic scar fibroblasts and block the downstream pathway, which may be one of the molecular mechanism of TGF-β1 in effecting hypertrophic scar formation.

关 键 词：增生性瘢痕 成纤维细胞 RHOA ROCK-I 结缔组织生长因子 

分 类 号：R318[医药卫生—生物医学工程]