Background and Aims: Recent research shows that abnormal expression of microRNA plays an important role in the process of hepatic fibrosis. miR-370 has been reported to be involved in liver function and is suppressed during hepatic carcinogenesis. The aim of this study was to investigate the role of miR-370 in hepatic fibrosis. Methods: The expression levels of miR-370 in rat fibrotic livers and activated hepatic stellate cells (HSCs) were evaluated by quantitative real-time PCR. The effect of miR-370 on the activation of HSCs was analyzed by flow cytometric analyses, real-time PCR and Western blot. Adenovirus carrying miR-370 was injected through the tail vein to access the effect of miR-370 on hepatic fibrosis induced by CCl4 in rats. The downstream targets of miR-370 were predicted by the Target Scan database and verified by luciferase assays, real-time PCR and Western blot in HSCs and were further confirmed by immunohistochemistry in vivo. Results: Real-time PCR showed that miR-370 expression was significantly reduced in rat fibrotic livers and TGFβ1-stimulated HSCs. Overexpression of miR-370 inhibited the proliferation of HSC-T6 cells via inducing cell apoptosis and suppressed the activation of HSCs. Upregulation of miR-370 obviously attenuated the CCl4-induced liver fibrosis in rats. miR-370 was directly bound to the 3′UTR of Smoothened (SMO) and suppressed the expression of SMO in HSCs and fibrotic livers. Conclusions: Our study demonstrated that miR-370 plays an inhibitory role in hepatic fibrogenesis by targeting SMO. Restoration of miR-370 may have beneficial effects on the treatment of liver fibrosis.
CITATION STYLE
Lu, C. H., Hou, Q. R., Deng, L. F., Fei, C., Xu, W. P., Zhang, Q., … Zhang, X. (2015). MicroRNA-370 Attenuates Hepatic Fibrogenesis by Targeting Smoothened. Digestive Diseases and Sciences, 60(7), 2038–2048. https://doi.org/10.1007/s10620-015-3585-0
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