Epigallocatechin Gallate Attenuated the Activation of Rat Cardiac Fibroblasts Induced by Angiotensin II via Regulating β-Arrestin1

Cellular Physiology and Biochemistry

关键词: Epigallocatechin gallate;    Myocardial remodeling;    Angiotensin II receptor;    β-arrestin;    Cardiac fibroblasts;   

DOI  :  10.1159/000343371

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Angiotensin II (AngII) activated cardiac fibroblasts (CFs) predominantly through AngII subtype 1a receptor (AT1aR). This study was carried out to explore the potential inhibitory effects and mechanisms of epigallocatechin gallate (EGCG) on AngII induced rat CFs. Methods Viability, proliferation and collagen production of CFs were measured by MTT assay, [³H]-thymidine and [³H]-proline incorporation respectively. β-arrestin1 (βarr1), AT1aR and AT1bR mRNA levels were determined by quantitative PCR. AT1R, Gq, βarr 1/2, phosphorylated kinase C (p-PKC)-delta expressions were detected by western blotting. We blocked βarr1 expression using βarr1 small interfering RNA (siRNA). Results EGCG inhibited the activation of CFs induced by AngII. βarr1 mRNA level revealed a positive correlation with the viability of CFs. SiRNA targeting βarr1 blocked the activation of CFs. In vitro, AngII increased βarr1 mRNA, total and membrane βarr1 protein expressions, but reduced AT1aR mRNA, global and membrane AT1R, total Gq and cytoplasmic p-PKC-delta levels. Administration of EGCG restored the above abnormalities, whereas Gq levels were not affected. Conclusion Our findings showed that βarr1 is essential for AngII-mediated activation of CFs. EGCG attenuated CFs activation induced by AngII via regulating βarr1 and thus, modulating AT1aR mediated signaling.

【 授权许可】

CC BY-NC-ND