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RhoA-Rho kinase signaling pathway mediates adventitial fibroblasts differentiation to myofibroblasts induced by TGF-β1

Chen Wen-Dong, Chu Yu-Feng, Liu Jian-Jun, Hong Mo-Na, Gao Ping-Jin

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； Laboratory of Vascular Biology, Institute of Health Science, Shanghai Institute for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China； Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.

Abstract

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.

Key words: adventitial fibroblast; myofibroblast; transforming growth factor β1; RhoA; Rho kinase

Received: 2012-07-31　　Accepted: 2012-09-21

Corresponding author: 高平进　　E-mail: gaopingjin@yahoo.com.cn

Citing This Article：

Chen Wen-Dong, Chu Yu-Feng, Liu Jian-Jun, Hong Mo-Na, Gao Ping-Jin . RhoA-Rho kinase signaling pathway mediates adventitial fibroblasts differentiation to myofibroblasts induced by TGF-β1. Acta Physiol Sin 2013; 65 (2): 113-121 (in Chinese with English abstract).