Rosiglitazone inhibits hepatic stellate cell proliferation by regulating peroxisome proliferator-activated receptor gamma/ heme oxygenase-1 expression

Abstract

Objective: To investigate the effect of rosiglitazone (RGZ) on the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and heme oxygenase-1 (HO-1) in hepatic stellate cells (HSCs). Methods: In vitro activated hepatic stellate cell-T6 (HSC-T6) as research subjects were divided into blank control group, RGZ intervention group, and RGZ + ZnPP-IX mutual intervention group. MTT colorimetry method was used to measure the condition of cell proliferation. ELISA was used to detect the content of hyaluronic acid (HA) and type III procollagen peptide (PIIIP) in the cell supernatant. Real-time quantative PCR, western blot and immunocytochemistry were used to detect the relative expression levels of PPARγ, HO-1 mRNA and protein. One-way analysis of variance was used to compare the sample mean between multiple groups, and LSD test was used for comparison between two groups. Results: The proliferation activity of HSC-T6 and the expressions of HA and PIIIP in the RGZ intervention group were significantly lower than those in the blank control group (P ​​< 0.01), but the relative expression levels of PPARγ and HO-1 mRNA and protein were significantly increased compared with the blank control group (PPARγ : 2.97 ± 0.22 vs. 1.07 ± 0.05, 0.96 ± 0.08 vs. 0.31 ± 0.03; HO-1: 4.28 ± 0.73 vs. 1.80 ± 0.36, 1.83 ± 0.26 vs. 0.61 ± 0.09), and the difference was statistically significant (P < 0.01). The proliferation activity of HSC-T6 and the expression of HA and PIIIP was higher in RGZ + ZnPP-IX mutual intervention group as compared with RGZ group (P < 0.05). HO-1 mRNA (3.16 ± 0.38 vs. 4.28 ± 0.73) and protein (1.31 ± 0.17 vs. 1.83 ± 0.26) relative expression levels was decreased, and the difference was statistically significant (P < 0.05). There was no statistically significant difference in the relative expression of PPARγ mRNA and protein (P > 0.05), however, there was a decreasing trend. HO-1 mRNA (1.80 ± 0.36) and protein (0.61 ± 0.09) relative expression was significantly increased in RGZ + ZnPP-IX group as compared to blank control group (P < 0.05). Immunocytochemical staining had consistency with the above results. Conclusion: The effect of rosiglitazone on inducing increased expression of PPARγ, and then inhibiting HSC proliferation activity and collagen production may be realized by regulating its downstream HO-1 expression.