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Aim:To investigate the effect of peroxisome proliferator-activated receptor gamma(PPARγ)activation on the growth of rat hepatic stellate cells(HSC)and trans-forming growth factor beta(TGF-β)-induced connective tissue growth factor(CTGF)expression.Methods:After being treated with various amounts of thePPARγ natural ligand 15-deoxy-A 12,14-prostaglandin J_2(15-d-PGJ_2)or syntheticligand GW7845,the status of HSC proliferation and apoptosis were detected byMTT assay and flow cytometry.Furthermore,HSC were treated with PPARγ-specific antagonist GW9662 prior to the addition of 15-d-PGJ_2 or GW7845 andwere subsequently stimulated with TGF-β1.The mRNA and protein levels ofCTGF expression were detected by semi-quantitative RT-PCR and Western blot-ting analysis.Morphological changes in the HSC were observed by electronmicroscopy.Results:15-d-PGJ_2 and GW7845 markedly inhibited HSC prolifera-tion and induced cell apoptosis in a dose-dependent manner.Furthermore,PPARγligands significantly suppressed TGF-β1-induced CTGF expression(at both tran-scriptional and post-transcriptional levels)in HSC,and the inhibitory effect wasdramatically,if not completely,abolished by pretreatment with GW9662,sug-gesting that the inhibition was indeed mediated by PPARγ.Moreover,morpho-logical observation revealed that PPARγ activation caused obvious changes ofHSC from activated to quiescent phenotype.Conclusion:The PPARγligand hasa potent inhibitory effect on the growth of HSC and TGF-β1-induced CTGFexpression,which makes it a potential antifibrotic candidate for the treatment andprevention of hepatic fibrosis.
Aim: To investigate the effect of peroxisome proliferator-activated receptor gamma (PPARγ) activation on the growth of rat hepatic stellate cells (HSC) and trans-forming growth factor beta (TGF-β) -induced connective tissue growth factor . Methods: After being treated with various amounts of the PPARγ natural ligand 15-deoxy-A 12,14-prostaglandin J_2 (15-d-PGJ_2) or syntheticligand GW7845, the status of HSC proliferation and apoptosis were detected by MTT assay and flow cytometry. HSC were treated with PPARγ-specific antagonist GW9662 prior to the addition of 15-d-PGJ_2 or GW7845 and subsequently stimulated with TGF-β1.The mRNA and protein levels of CTGF expression were detected by semi-quantitative RT-PCR and Western blot -ting analysis. Morphological changes in the HSC were observed by electron microscopy. Results: 15-d-PGJ_2 and GW7845 markedly inhibited HSC prolifera- tion and induced cell apoptosis in a dose-dependent manner. Thermore, PPARγ signaling and significantly su ppressed TGF-β1-induced CTGF expression (at both tran-scriptional and post-transcriptional levels) in HSC, and the inhibitory effect wasdramatically, if not completely, abolished by pretreatment with GW9662, sug-gesting that the inhibition was indeed mediated by PPARγ . Moreover, morpho-logical observation revealed that PPARγ activation caused significant changes of HSC from activated to quiescent phenotype. Contact: The PPARγligand hasa potent inhibitory effect on the growth of HSC and TGF-β1-induced CTGFexpression, which makes it a potential antifibrotic candidate for the treatment andprevention of hepatic fibrosis.