MicroRNA-451 and Genistein Ameliorate Nonalcoholic Steatohepatitis in Mice

MicroRNA-451 和染料木黄酮改善小鼠非酒精性脂肪性肝炎

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作者:Mailin Gan, Linyuan Shen, Yuan Fan, Ya Tan, Ting Zheng, Guoqing Tang, Lili Niu, Ye Zhao, Lei Chen, Dongmei Jiang, Xuewei Li, Shunhua Zhang, Li Zhu

Abstract

Effective, targeted therapy for chronic liver disease nonalcoholic steatohepatitis (NASH) is imminent. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for liver disease. Here, we investigated the functional role of miR-451 and the therapeutic effects of genistein in the NASH mouse model. MiR-451 was downregulated in various types of liver inflammation, and subsequent experiments showed that miR-451 regulates liver inflammation via IL1β. Genistein is a phytoestrogen with anti-inflammatory and anti-oxidant effects. Interestingly, we found that the anti-inflammatory effects of genistein were related to miR-451 and was partially antagonized by the miR-451 inhibitor. MiR-451 overexpression or genistein treatment inhibited IL1β expression and inflammation. Taken together, this study shows that miR-451 has a protective effect on hepatic inflammation, and genistein can be used as a natural promoter of miR-451 to ameliorate NASH.

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