RhoA- Rho激酶信号通路介导转化生长因子-β1诱导的外膜成纤维细胞向肌成纤维细胞分化。
RhoA-Rho kinase signaling pathway mediates adventitial fibroblasts differentiation to myofibroblasts induced by TGF-β1.
作者信息
Chen Wen-Dong, Chu Yu-Feng, Liu Jian-Jun, Hong Mo-Na, Gao Ping-Jin
机构信息
State Key Laboratory of Medical Genomics and Shanghai Key Laboratory of Vascular Biology at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
出版信息
Sheng Li Xue Bao. 2013 Apr 25;65(2):113-21.
Vascular adventitial fibroblasts (AF) differentiation to myofibroblasts (MF) is the critical physiopathologic feature of vascular remodeling. This study was to investigate the role of RhoA-Rho kinase signaling pathway in AF differentiation to MF induced by transforming growth factor β1 (TGF-β1). The results showed that TGF-β1 up-regulated total RhoA protein expression and RhoA activity in cultured AF by Western blotting and Rho pull-down assay, respectively. TGF-β1 up-regulated phospho-Myosin phosphatase target subunit (MYPT1, a downstream substrate of Rho kinase) expression without altering Rho kinase protein expression, indicating TGF-β1 induced the enhancement of activity of Rho kinase. Ad-N19RhoA-hrGFP virus infection and Y27632, a specific inhibitor of Rho kinase, dose-dependently inhibited TGF-β1-induced α-SM-actin and Calponin expression, as markers of MF differentiation. In conclusion, the RhoA-Rho kinase pathway is involved in AF differentiation to MF induced by TGF-β1.
血管外膜成纤维细胞（AF）向肌成纤维细胞（MF）的分化是血管重塑的关键病理生理特征。本研究旨在探讨RhoA-Rho激酶信号通路在转化生长因子β1（TGF-β1）诱导的AF向MF分化中的作用。结果显示，通过蛋白质免疫印迹法和Rho下拉试验分别发现，TGF-β1上调了培养的AF中RhoA总蛋白表达和RhoA活性。TGF-β1上调了肌球蛋白磷酸酶靶向亚基（MYPT1，Rho激酶的下游底物）的磷酸化表达，而未改变Rho激酶蛋白表达，表明TGF-β1诱导了Rho激酶活性增强。Ad-N19RhoA-hrGFP病毒感染以及Rho激酶特异性抑制剂Y27632均剂量依赖性地抑制了TGF-β1诱导的α-平滑肌肌动蛋白和钙调蛋白表达，这两种蛋白是MF分化的标志物。总之，RhoA-Rho激酶通路参与了TGF-β1诱导的AF向MF的分化。
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