MiR-34a promotes fibrosis of hepatic stellate cells via the TGF-β pathway.

Abstract

BackgroundPrevious studies have confirmed that MicroRNA (miRNA) is a key regulator exhibiting different effects in human liver fibrosis. However, the function of miR-34a in liver fibrosis has not been reported. Hence, this study aimed to investigate the regulatory mechanism of miR-34a in liver fibrosis.MethodsThe expression of miR-34a was measured in fibrosis tissues via the quantitative real-time PCR (qRT-PCR) assay. Subsequently, 30 male C57BL/6J mice were divided into control and treatment groups and used to establish animal models of liver fibrosis to explore the expression level of miR-34a. Moreover, Cell Counting Kit 8 (CCK-8) and transwell assays were preformed to identify the regulatory mechanism of miR-34a in cells. The effect of miR-34a on the activity of transforming growth factor-β (TGF-β) pathway was observed by western blot.ResultsUp-regulation of miR-34a was detected in fibrosis cells. Moreover, the cellular phenotype was suppressed by miR-34a down-regulation in a primary culture of hepatic stellate cells (HSCs). Besides, it was found that increased miR-34a could significantly promote the invasion and migration of HSCs. Moreover, miR-34a activates HSCs through transforming TGF-β, α-smooth muscle actin (α-SMA), and Monocyte chemoattractant protein-1 (MCP-1), which further affects liver fibrosis.ConclusionsMiR-34a promotes the fibrosis of HSCs as well as cell proliferation, migration, and invasion.