title: RhoA-Rho kinase signaling pathway mediates adventitial fibroblasts differentiation to myofibroblasts induced by TGF-β1.
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.
authors.affiliation: 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.
authors.forename: Wen-Dong
authors.initials: WD
authors.lastname: Chen
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Chu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Mo-Na
authors.initials: MN
authors.lastname: Hong
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D000199:Actins / Q000378:metabolism; D063194:Adventitia / Q000166:cytology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D008840:Microfilament Proteins / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000096985:Calponins
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D053773:Transforming Growth Factor beta1; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000096985:Calponins