Effects of all-trans retinioc acid on expressions of COL1α2, MMP-2, TIMP-1, and signaling pathway in TGF-β1-simulated rat hepatic stellate cells

Objective: To investigate the effects of all-trans retinioc acid (ATRA) on proliferation of rat hepatic stellate cells (HSC-T6) and expressions of collagen I, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-1 (TIMP-1) and signal protein Smad2/3 in TGF-β1-simulated HSC-T6 so as to explore the impact and molecular mechanisms of ATRA on liver fibrosis in vitro. Methods: Cultured HSC-T6s were treated with different concentrations of ATRA (0.1, 1, 10 μmol/L) for fixed time (12, 24, 48 hours). After intervention time, cell proliferation was evaluated by MTT. Meanwhile, HSC-T6s stimulated by TGF-β1 (5 ng/mL) were treated with different concentrations of ATRA for 24 h. The mRNA expressions of COL1α2, MMP-2 and TIMP-1 were quantified by RT-PCR; the expression of Smad 2/3 protein was determined by cell immunochemistry. Results: The proliferation of hepatic stellate cells was inhibited by ATRA in a dose-dependent manner (P<0.05). After induced by TGF-β1, the mRNA expressions of COL1α2, MMP-2 and TIMP-1 and the expression of Smad 2/3 protein were increased significantly compared with control group (P<0.05). However, ATRA could obviously reduce the mRNA expressions of COL1α2, MMP-2 and TIMP-1 and the expression of Smad 2/3 protein in HSC-T6 induced by TGF-β1 (P<0.05). Conclusion: ATRA can inhibit the proliferation of HSC-T6s and reduce the mRNA expressions of COL1α2, MMP-2 and TIMP-1 in HSC-T6 which were induced by TGF-β1. The anti-hepatic fibrosis function of ATRA may be related to its inhibition on the expression of Smad 2/3 protein in HSC-T6 to influence TGF-β1/Smad signaling pathway.