Repression of liver cirrhosis achieved by inhibitory effect of miR-454 on hepatic stellate cells activation and proliferation via Wnt10a.

Background: As is known, hepatic stellate cells (HSC) activation contributes to liver cirrhosis. This study aims to find out the acting mechanisms of miR-454 inhibiting the activation and proliferation of hepatic stellate cells.

Methods: The expression of Col1A1, α-SMA and Wnt10a were determined by western blot, and the miR-454 level was determined by qRT-PCR in this study. We took two objects as experiment subjects, one was liver cirrhosis rats, and the other was TGF-β1-stimulated HSC-T6 cells. After activated with TGF-β1 and transfected with miRNA-454 mimic, separately or successively, the changes on the Col1A1 and α-SMA expression, HSC proliferation, miR-454 level and Wnt10a expression were examined in HSC-T6 cells, respectively. Interaction between miR-454 and Wnt10a was evaluated with dual luciferase reporter assay.

Results: MiR-454 expression was down-regulated in tissues of liver cirrhosis rats. TGF-β1 caused the down-regulation of the miR-454 in HSC-T6 cells. MiR-454 inhibited the activation and proliferation of HSC-T6 cells. Wnt10a had a targeting relationship with miR-454. TGF-β1 promoted HSC-T6 activation and proliferation via down-regulating miR-454 expression, which further up-regulated Wnt10a expression. MiR-454 mimic inhibited cirrhosis progression in liver cirrhosis rats.

Conclusion: MiR-454 can inhibit the activation and proliferation of hepatic stellate cells via suppressing the expression of Wnt10a, to restrain liver cirrhosis.