A specific ligand of peroxisome proliferator-activated receptor gamma suppressing activation of hepatic stellate cells

Abstract

Objective To study the effect of rosiglitazone,a specific ligand of peroxisome proliferator-activatcd receptor gamma (PPARγ),on the biological characters of activation hepatic stellate cells (HSCs).Methods The activated HSCs were divided into four groups:control,3 μM rosiglitazone group,10 μM rosigtitazone group and 20μM rosiglitazone group.The cell proliferation was determined with MTT colorimetric assay.The expression at mRNA level of PPARγ,TGF-β1,and type Ⅰpro-collagen was detected by RT-PCR.The expression of proteins of PPARγ,TGF-β1,type Ⅰ and Ⅲcollagen was detected by Western blot.α-smooth muscle actin (α-SMA) of HSCs was detected with immunocytochemistry.Type Ⅰ collagen in the supernatant of cultured HSCs was measured by EIASA.Results 1)The expression of PPARγ at mRNA level markedly increased in HSCs of 20 μM and 10 μM rosiglitazone group than 3 μM and control group (P＜0.01),while typeⅠ pro-collagen decreased in HSCs of 20 μM and 10 μM rosiglitazone group (P＜0.01).The difference of the expression of PPARγ and type Ⅰ pro-collagen at mRNA level was not significant between 10 μM rosiglitazone group and 20 μmol/L rosiglitazone group(P＞0.05).Neither was it between control and3 μM rosiglitazone group(P＞0.05).2)The expression of proteins of PPART,TGF-β1 and type Ⅰ collagen was accordant with that of mRNA.The expression of type Ⅲ was not significantly different among the 4 groups(P＞0.05).3)The staining of α-SMA in HSCs markedly decreased in 20 μM and 10 μM rosiglitazone group than that of control and 3 μM rosiglitazone group(P＜0.05).There was no significant difference between 20μM and 10μM rosiglitazone group.Neither was it between 10μM rosiglitazone group and control group(P＞0.05).4)Type Ⅰ collagen in the supernatant of cultured HSCs in 20μM and 10 μM rosiglitazone group markedly decreased than that in control and 3 μM rosiglitazone group(P＜0.01).There was no significant difference between 20μM and 10μM rosiglitazone group.Neither was it between 10μM rosiglitazone group and control group(P＞0.05).Conclusion By increasing expression of PPARγ in activated HSCs,roziglitazone,a specific agonist of PPARγ,decreases α-SMA expression and collagen synthesis,inhibits proliferation and attenuates the production of type Ⅰ collagen.These results demonstrated that the activation of HSCs can be suppressed. Key words: Liver cirrhosis; Peroxisome proliferator-activated receptor gamma; Ligand; Rosiglitazone; Hepatic stellate cell