1. Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-β1 pathway
- Author
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Yunping Chen, Shuzhi Li, Jingquan Gao, Qianhui Zhang, Lina Ba, Hongli Sun, Ye Wang, Wei Huang, Mingyao E, Pilong Shi, Yonggang Cao, Yan Liu, and Hanping Qi
- Subjects
0301 basic medicine ,Pharmacology ,Pressure overload ,medicine.medical_specialty ,Cyclin E ,biology ,Chemistry ,Cardiac fibrosis ,Cyclin-dependent kinase 2 ,General Medicine ,Transforming growth factor beta ,medicine.disease ,Angiotensin II ,Calcium in biology ,03 medical and health sciences ,Transient receptor potential channel ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,030220 oncology & carcinogenesis ,Internal medicine ,cardiovascular system ,medicine ,biology.protein - Abstract
Cardiac fibrosis is a common pathologic change along with pressure overload. Recent studies indicated that transient receptor potential (TRP) channels played multiple roles in heart. However, the functional role of transient receptor potential vanilloid-3 (TRPV3) in cardiac fibrosis remained unclear. The present study was designed to investigate the relationship between TRPV3 activation and pressure overload-induced cardiac fibrosis. Pressure overload rats were successfully established by abdominal aortic constriction (AAC), and cardiac fibrosis was simulated by 100 nM angiotensin II (Ang II) in neonatal cardiac fibroblasts. Echocardiographic parameters, cardiac fibroblast proliferation, cell cycle, intracellular calcium concentration ([Ca2+] i ), and the protein expressions of collagen I, collagen III, transforming growth factor beta 1 (TGF-β1), cyclin E, and cyclin-dependent kinase 2 (CDK2) were measured. Echocardiographic and histological measurements suggested that the activation of TRPV3 exacerbated the cardiac dysfunction and increased interstitial fibrosis in pressure overload rats. Further results showed that TRPV3 activation upregulated the expressions of collagen I, collagen III, TGF-β1, cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-β1 pathway could partially reverse the effect of TRPV3 activation. These results suggested that TRPV3 activation exacerbated cardiac fibrosis by promoting cardiac fibroblast proliferation through TGF-β1/CDK2/cyclin E pathway in the pressure-overloaded rat hearts.
- Published
- 2017
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