Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-ß1 pathway.
Naunyn Schmiedebergs Arch Pharmacol
; 391(2): 131-143, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29249037
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-ß1), 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-ß1, cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-ß1 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-ß1/CDK2/cyclin E pathway in the pressure-overloaded rat hearts.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Canais de Cátion TRPV
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Fator de Crescimento Transformador beta1
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Miocárdio
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article