MicroRNA-24-3p alleviates hepatic ischemia and reperfusion injury in mice through the repression of STING signaling

Biochem Biophys Res Commun. 2020 Jan 29;522(1):47-52. doi: 10.1016/j.bbrc.2019.10.182. Epub 2019 Nov 14.

Abstract

Ischemia and reperfusion (I/R) injury is a common cause of hepatocyte injury and liver dysfunction during liver transplantation, but its mechanism is needed further explored. We aimed to investigate whether STING pathway activation is involved in the liver I/R and further determine the role of the microRNA(miR)-24-3p in liver I/R injury in mice. Our data showed that STING mRNA level was negatively related with miR-24-3p in livers of I/R-treated mice. Next, we identified that STING could be bound by miR-24-3p by bioinformatic and luciferase report assay. Moreover, downregulation of STING alleviated the protein expression of p-IRF3 and the serum level of inflammatory factor and aminotransferase in I/R mice model. Furthermore, transfection of I/R treated mice with exogenous miR-24-3p significantly inhibited the protein expression of STING and p-IRF3 in liver, and attenuated serum inflammatory cytokines release, as well as the dysfunction and apoptosis of liver in I/R model in vivo. This study suggests that miR-24-3p may ameliorate inflammatory response and cellular apoptosis in hepatic I/R process by targeting STING, which might be a potential therapeutic target for preventing liver I/R development and progression.

Keywords: Inflammation; Interferon regulatory factor 3; Liver ischemia and reperfusion injury; MicroRNA-24-3p; Stimulator of interferon genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Disease Progression
  • Gene Expression Regulation*
  • Inflammation
  • Interferon Regulatory Factor-3 / metabolism
  • Liver / metabolism
  • Liver / pathology*
  • Liver Diseases / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • MicroRNAs / metabolism*
  • Reperfusion Injury / pathology*

Substances

  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Membrane Proteins
  • MicroRNAs
  • Mirn24 microRNA, mouse
  • Sting1 protein, mouse