Loureirin B inhibits the proliferation of hepatic stellate cells and the Wnt/β-catenin signaling pathway by regulating miR-148-3p

龙血素B通过调控miR-148-3p抑制肝星状细胞增殖及Wnt/β-catenin信号通路

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作者:Jian-Peng Hu #, Rong Zhang #, Min Tang, Yu-Lian Li, Lin-Ting Xun, Zhi-Zhou Shi, Ying An, Ting Li, Zheng-Ji Song

Background

We investigated the activity of loureirin B against liver fibrosis and the underlying molecular mechanisms.

Conclusion

Our results suggest that loureirin B inhibited the proliferation and promoted the apoptosis of HSCs, and suppressed the Wnt/β-catenin signaling pathway via regulation of miR-148-3p.

Methods

Hepatic stellate cells (HSCs) from Sprague-Dawley rats were treated with different concentrations of loureirin B. We used the MTT assay to determine HSC proliferation, flow cytometry to analyze apoptosis, and western blot to determine the expressions of Bax, Bcl-2, Wnt1 and β-catenin. Real-time PCR was used to determine the expressions of Wnt1 and miR-148-3p.

Results

The MTT assay showed that loureirin B treatment significantly inhibited the proliferation of HSCs in time- and dose-dependent manners. Loureirin B significantly promoted the apoptosis of HSCs, increased the expression of Bax and decreased the Bcl-2 level. Western blot analysis showed that the expressions of Wnt1 and β-catenin were obviously lower in the loureirin B treatment group than in the control group. We also found that loureirin B could decrease the Wnt1 mRNA level and increase miR-148-3p expression. Knockdown of miR-148-3p using inhibitor could reverse the effects of loureirin B on the proliferation and apoptosis of HSCs and the expressions of Bax, Bcl-2, Wnt1 and β-catenin.

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