Effect of ligand of peroxisome proliferator-activated receptor γ on the biological characters of hepatic stellate cells

AIM: To study the effect of rosiglitazone, which is a ligand of peroxisome proliferator-activated receptor gamma (PPAR gamma), on the expression of PPAR gamma in hepatic stellate cells (HSCs) and on the biological characteristics of HSCs. METHODS: The activated HSCs were divided into three groups: control group, 3 mu mol/L rosiglitazone group, and 10 mu mol/L rosiglitazone group. The expression of PPAR gamma, alpha-smooth muscle actin (alpha-SMA), and type I and III collagen was detected by RT-PCR, Western blot and immunocytochemical staining, respectively. Cell proliferation was determined with methylthiazolyltetrazolium (MTT) colorimetric assay. Cell apoptosis was demonstrated with flow cytometry. RESULTS: The expression of PPAR gamma at mRNA and protein level markedly increased in HSCs of 10 mu mol/L rosiglitazone group (t value was 10.870 and 4.627 respectively, P<0.01 in both). The proliferation of HSCs in 10 mu mol/L rosiglitazone group decreased significantly (t = 5.542, P<0.01), alpha-SMA expression level and type I collagen synthesis ability were also reduced vs controls (t value = 10.256 and 14.627 respectively, P<0.01 in both). The apoptotic rate of HSCs significantly increased in 10 mu mol/L rosiglitazone group vs control (chi(2) = 16.682, P<0.01). CONCLUSION: By increasing expression of PPAR gamma in activated HSCs, rosiglitazone, an agonist of PPAR gamma, decreases alpha-SMA expression and type I collagen synthesis, inhibits cell proliferation, and induces cell apoptosis. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.