The effect of saraglitazar on TGF-β-induced smad3 phosphorylation and expression of genes related to liver fibrosis in LX2 cell line.

Abstract

Liver fibrosis is a reversible liver injury that occurs as a result of many chronic inflammatory diseases and can lead to cirrhosis, which is irreversible and fatal. So, we studied the anti-fibrotic effects of saroglitazar on LX-2 cell lines, as a dual PPARα/γ agonist. Cells, after 80% confluence, were treated with TGF-β (2 ng/mL) for 24h. Then cells were treated with saroglitazar at different doses (2.5, 5, 10 µM) for 24h. After same incubation, the cells of control group, TGF-β group, and TGF-β + saroglitazar group were harvested for RNA and protein extraction to determine the effects of saroglitazar. RT-PCR and western blot methods were used to express genes related to fibrosis. Our results show that the relative expression of α-SMA, collagen1α, N-cadherin, NOX (1, 2, and 4), and phosphorylated Smad3 protein was significantly higher in TGF-β-treated cells compared with the normal group, and E-cadherin expression was decreased in TGF-β-treated cells. After TGF-β-treated cells were exposed to saroglitazar, the expression of these genes was significantly reversed (P < 0.05). Our results clearly show the short-term inhibitory role of saroglitazar in the expression of fibrotic factors using the TGF-β/Smad signaling pathway. These results suggest that saroglitazar can be considered as a suitable therapeutic strategy for fibrotic patients. Although more studies are needed.