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, 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.
Zhang
Huijie
H
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, PR China.
Pi
Rongbiao
R
Li
Ruifang
R
Wang
Ping
P
Tang
Futian
F
Zhou
Sigui
S
Gao
Jie
J
Jiang
Jianmin
J
Chen
Shaorui
S
Liu
Peiqing
P
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology*; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology
D024042:Collagen Type I; C425931:GW 501516; D047494:PPAR delta; D048068:PPAR-beta; D013844:Thiazoles; D000804:Angiotensin II