[Peroxisome proliferator-activated receptor gamma inhibits transforming growth factor beta1-induced connective tissue growth factor expression in rat hepatic stellate cells].
OBJECTIVE
To investigate the effect of peroxisome proliferator-activated receptor gamma (PPARgamma) activation on transforming growth factor beta1 (TGF-beta1)-induced connective tissue growth factor (CTGF) expression in rat hepatic stellate cells (HSCs).


METHODS
Cultured HSCs with or without PPARgamma-specific antagonist GW9662 treatment prior to the addition of an increasing amount of PPARgamma natural ligand (15-d-PGJ2) or synthetic ligand (GW7845) were stimulated with TGF-beta1. The mRNA and protein levels of CTGF expression were detected by semi-quantitative RT-PCR and Western blotting, respectively. The morphological changes of the HSC were observed by electron microscope.


RESULTS
15-d-PGJ2 and GW7845 significantly inhibited TGF-beta1-induced CTGF expression at both mRNA and protein levels in HSCs, and the inhibitory effect was dramatically, if not completely, abolished by pretreatment with GW9662, suggesting that the inhibition was mediated by PPARgamma. Morphological observation revealed that PPARgamma activation caused obvious changes of HSCs from activated to quiescent phenotypes.


CONCLUSIONS
PPARgamma ligand shows potent inhibitory effect on TGF-beta1-induced CTGF expression in rat HSCs, suggesting its potential as a candidate agent for treatment and prevention of hepatic fibrosis.
Sun
Kai
K
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. sunkai9602@sina.com
Huang
Xiao-Hui
XH
Wang
Qian
Q
D000818:Animals; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D047495:PPAR gamma / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
C526316:CCN2 protein, rat; D010080:Oxazoles; D047495:PPAR gamma; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; C401311:GW 7845; D014443:Tyrosine