Fibrosis is the common results from an excessive wound-healing response to chronic liver injury. Otreotide (OCT), an analogue of somatostatin, was reported to have an anti-hepatic fibrosis effect. However, its anti-fibrosis mechanisms have not been well characterized to date. The present study aimed to investigate the protective effects of OCT on carbon tetrachloride (CCl4)-induced rat liver fibrosis and activation and proliferation of transforming growth factor-β1 (TGF-β1)-treated hepatic stellate cells (HSCs) and explore its anti-hepatofibrotic mechanisms. Our results indicated that treatment with OCT markedly down-regulated the protein and mRNA expression of liver fibrosis markers including α-smooth muscle actin (α-SMA) and collagen I in CCl4-induced rat model of liver fibrosis, accompanied by decreasing aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL) activities and increasing the serum level of albumin (ALB). In addition, in vitro results revealed that OCT inhibited the activation and proliferation of TGF-β1-treated LX-2 cells in a concentration-dependent manner and decreased in parallel the expression of Wnt1, β-catenin, c-Myc and cyclin D1, indicating that OCT might attenuate liver fibrosis, at least in part, by inhibiting Wnt/β-catenin signaling pathway. Overall, these results provide a novel anti-fibrotic mechanism of OCT, which might be associated with its ability to repress Wnt/β-catenin signaling pathway.
Keywords: C-Myc; Cyclin D1; Hepatic fibrosis; Octreotide; Wnt/β-catenin; α-SMA.
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