MicroRNA-451 and Genistein Ameliorate Nonalcoholic Steatohepatitis in Mice

Int J Mol Sci. 2019 Dec 3;20(23):6084. doi: 10.3390/ijms20236084.

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.

Keywords: NASH; genistein; hepatocarcinoma; miR-451.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Diet, High-Fat
  • Down-Regulation / genetics
  • Female
  • Genistein / pharmacology
  • Genistein / therapeutic use*
  • Humans
  • Inflammation / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides
  • Liver / pathology
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Mice, Inbred ICR
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / genetics*

Substances

  • Interleukin-1beta
  • Lipopolysaccharides
  • MicroRNAs
  • Mirn451 microRNA, mouse
  • Genistein