PPARbeta/delta activation inhibits angiotensin II-induced collagen type I expression in rat cardiac fibroblasts

Peroxisome proliferator-activated receptors (PPARalpha, beta/delta and gamma) are nuclear receptors and PPARgamma activation was previously reported to inhibit collagen expression in the heart, but whether PPARbeta/delta also regulates collagen expression in the heart remains unclear. In this study,...

Full description

Saved in:
Bibliographic Details
Published in:Archives of biochemistry and biophysics 2007-04, Vol.460 (1), p.25-32
Main Authors: Zhang, Huijie, Pi, Rongbiao, Li, Ruifang, Wang, Ping, Tang, Futian, Zhou, Sigui, Gao, Jie, Jiang, Jianmin, Chen, Shaorui, Liu, Peiqing
Format: Article
Language:English
Subjects:
Angiotensin II - antagonists & inhibitors
Angiotensin II - pharmacology
Animals
Collagen Type I - metabolism
Dose-Response Relationship, Drug
Fibroblasts - drug effects
Fibroblasts - metabolism
Male
Myocardium - cytology
PPAR delta - agonists
PPAR delta - metabolism
PPAR-beta - agonists
PPAR-beta - metabolism
Rats
Rats, Sprague-Dawley
RNA Interference
Thiazoles - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Peroxisome proliferator-activated receptors (PPARalpha, beta/delta and gamma) are nuclear receptors and PPARgamma activation was previously reported to inhibit collagen expression in the heart, but whether PPARbeta/delta also regulates collagen expression in the heart remains unclear. In this study, we investigated the effect of PPARbeta/delta activation on angiotensin II (Ang II)-induced collagen type I expression in adult rat cardiac fibroblasts. The results showed that PPARbeta/delta was expressed at the moderate level in cardiac fibroblasts. GW501516, a selective PPARbeta/delta agonist, depressed Ang II-stimulated collagen type I expression and collagen synthesis in cardiac fibroblasts in a concentration-dependent manner. Furthermore, these inhibitory effects of GW501516 were completely reversed by the knockdown of PPARbeta/delta via RNA interference. In summary, we find that PPARbeta/delta is present in cardiac fibroblasts and PPARbeta/delta activation inhibits Ang II-induced collagen type I expression at least in part via decreasing collagen synthesis. PPARbeta/delta may be a promising therapeutic target for myocardial fibrosis.
ISSN:0003-9861