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[Peroxisome proliferator-activated receptor gamma inhibits transforming growth factor beta1-induced connective tissue

Kai Sun1, Xiao-Hui Huang, Qian Wang

  • 1Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. sunkai9602@sina.com

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University
|July 22, 2009
PubMed
Abstract

Insights

Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits transforming growth factor beta1 (TGF-beta1)-induced connective tissue growth factor (CTGF) in rat hepatic stellate cells. This suggests PPARgamma ligands may treat hepatic fibrosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Hepatology

Background:

  • Hepatic stellate cells (HSCs) play a critical role in liver fibrosis.
  • Transforming growth factor beta1 (TGF-beta1) is a key mediator in HSC activation and fibrosis.
  • Connective tissue growth factor (CTGF) is implicated in the pathogenesis of liver fibrosis.

Purpose of the Study:

  • To investigate the effect of peroxisome proliferator-activated receptor gamma (PPARgamma) activation on TGF-beta1-induced CTGF expression in rat HSCs.
  • To determine if PPARgamma ligands can modulate CTGF production in activated HSCs.
  • To explore the potential of PPARgamma as a therapeutic target for hepatic fibrosis.

Main Methods:

  • Rat HSCs were cultured and treated with PPARgamma ligands (15-d-PGJ2, GW7845) or a PPARgamma antagonist (GW9662).
  • Cells were stimulated with TGF-beta1, and CTGF expression was measured at mRNA and protein levels using RT-PCR and Western blotting.
  • Morphological changes in HSCs were assessed via electron microscopy.

Main Results:

  • PPARgamma ligands significantly inhibited TGF-beta1-induced CTGF expression at both mRNA and protein levels in HSCs.
  • The inhibitory effect of PPARgamma ligands was reversed by the PPARgamma antagonist GW9662.
  • PPARgamma activation induced morphological changes in HSCs, shifting them from an activated to a quiescent phenotype.

Conclusions:

  • PPARgamma activation potently inhibits TGF-beta1-induced CTGF expression in rat HSCs.
  • This inhibition suggests that PPARgamma ligands may be effective agents for the treatment and prevention of hepatic fibrosis.
  • PPARgamma activation promotes HSC quiescence, contributing to its antifibrotic effects.

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