MicroRNA-370 Attenuates Hepatic Fibrogenesis by Targeting Smoothened
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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.
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.
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.
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.
KeywordsmiR-370 Hepatic fibrosis Smoothened Hedgehog signal
This work was supported by the National Natural Science Foundation of China (81372675), Shanghai Science and Technology Committee for Key Projects (13JC1407401) and Foundation for Talents in Six Fields of Jiangsu Province (no. 2011-WS- 061).
Conflict of interest
- 26.Li L, Li G, Yu C, et al. A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting transforming growth factor-beta receptor II. Liver Int. 2014. doi: 10.1111/liv.12441.