MiR-142-3p blocks TGF-β-induced activation of hepatic stellate cells through targeting TGFβRI

Aim: To understand the contribution of miR-142-3p in the activation of hepatic stellate cells (HSCs) and liver fibrosis, and the underlying mechanism. Materials and methods: We detected microRNAs expression profiles in quiescent and activated HSCs by microRNA-array, and performed qRT-PCR to validate these data in HSCs and plasma of cirrhosis patients. In vitro, the 3rd-5th passage HSCs was transfected with mir-142-3p mimics or stimulated with TGF beta. The markers of HSCs activation (i.e. FN and alpha-SMA) were examined by qRT-PCR and western blotting, and cell viability was detected by MTT, colony formation assays respectively. Key finding: In our study, we identified miR-142-3p as a novel regulator of HSCs activation and indicator of hepatic cirrhosis. We found that miR-142-3p was significantly reduced in activated HSCs, while TGF beta RI was distinctly up-regulated in activated HSCs. Ectopic expression of miR-142-3p in activated HSCs inhibited cell viability as well as cell growth, and blocked HSCs activation, concomitant with decreased transdifferentiation markers (i.e. FN and a-SMA). Further, we confirmed that miR-142-3p was reduced upon TGF-beta exposure, while diminishing TGF-beta-Smad signaling pathway in turn by reducing TGF beta RI expression in HSCs. Besides, the plasma level of miR-142-3p declined significantly in patients with hepatic cirrhosis. Significance: In conclusion, we demonstrated that miR-142-3p repressed TGF-beta-Smad signaling pathway to prevent HSCs activation through directly targeting TGF beta RI in HSCs.