title: STAT3 Protein Regulates Vascular Smooth Muscle Cell Phenotypic Switch by Interaction with Myocardin.
abstract: The JAK-STAT3 signaling pathway is one of the critical pathways regulating cell proliferation, differentiation, and apoptosis. Myocardin is regarded as a key mediator for the change of smooth muscle phenotypes. However, the relationship between STAT3 and myocardin in the vascular smooth muscle cell (VSMC) phenotypic switch has not been investigated. The goal of this study was to investigate the molecular mechanism by which STAT3 affects the myocardin-regulated VSMC phenotypic switch. Data presented in this study demonstrated that STAT3 was rapidly up-regulated after stimulation with VEGF. Inhibition of the STAT3 activation process impaired VSMC proliferation and enhanced the expression of VSMC contractile genes by increasing serum-response factor binding to the CArG-containing regions of VSMC-specific contractile genes. In contrast, the interaction between serum-response factor and its co-activator myocardin was reduced by overexpression of STAT3. In addition, treated VEGF inhibited the transcription activity of myocardin, and overexpression of STAT3 inhibited myocardin-induced up-regulation of VSMC contractile phenotype-specific genes. Although myocardin and STAT3 are negatively correlated, interestingly, both of them can enhance the expression of VEGF, suggesting a feedback loop to regulate the VSMC phenotypic switch. Taken together, these results indicate that the JAK-STAT3 signaling pathway plays a key role in controlling the phenotypic switch of VSMCs through the interactions between STAT3 and myocardin by various coordinated gene regulation pathways and feedback loops.
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430000 and the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Liao
authors.affiliation: the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Dong-Wei
authors.initials: DW
authors.lastname: Zhao
authors.affiliation: the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: De-Liang
authors.initials: DL
authors.lastname: Zheng
authors.affiliation: the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xing
authors.affiliation: the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Ma
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430000 and.
authors.forename: Le-Yuan
authors.initials: LY
authors.lastname: Bao
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430000 and.
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430000 and the Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China zhangtongcun@wust.edu.cn tony@tust.edu.cn.
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000099251:Myocardin
chemical_list: D053612:Janus Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; D026362:Serum Response Factor; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D000099251:Myocardin; C476858:SRF protein, human; C494086:STAT3 protein, human; C467484:VEGFA protein, human; C535150:MAPK1 protein, human
keywords: cardiovascular; cardiovascular disease; cell signaling; transcription factor; transcription regulation