Altered miR-370 expression in hepatic ischemia-reperfusion injury correlates with the level of nuclear kappa B (NF-κB) related factors

Gene. 2017 Apr 5:607:23-30. doi: 10.1016/j.gene.2016.12.026. Epub 2016 Dec 30.

Abstract

Background & aims: MicroRNAs (miRNAs) are a class of small endogenous, non-coding RNAs that regulate gene expression at both the transcription and translation levels. Whether miRNAs have taken part in liver ischemia-reperfusion (IR) injury was rarely reported. The purpose of this article is to investigate the potential role of miR-370 in hepatic IR injury.

Methods: Male C57BL/6 mice were divided into 5 groups (sham-operated group, I/R group, IPC group, antagomir-370 group and antagomir-NC), and the expression levels of miR-370 were assessed by quantitative real-time PCR. Serum enzyme analysis and histological examination of liver were used as the index of the effect of miR-370 on hepatic IR injury and following treatment of mice with antagomir-370 or antagomir-NC. The classical pathway factors of NF-κB (TAK1, TAB1, TAB2, IkBα, IKKα, IKKβ, p50, p65) were studied by quantitative real-time PCR and Western blot.

Results: The results showed that the IR group's miR-370 expression level was significantly upregulated as compared with the sham-operated group and IPC group. Also inhibition of miR-370 led to the low expression levels of miR-370 and low levels of serum aminotransferase and hepatic histological damage as compared with the IR group. Quantitative real-time PCR showed the levels of TAK1, TAB1, TAB2, IkBα, IKKα, p65 was elevated when improving the miR-370 levels, at the same time, Western blot showed the levels of TAK1, TAB1, TAB2, IkBα, IKKα, IKKβ, p50, p65 were all elevated.

Conclusion: miR-370 acting via NF-κB might play a crucial role in hepatic IR injury, and inhibition of miR-370 could alleviate the injury to the liver. And miR-370 might positively regulated the NF-κB pathway.

Keywords: Injury; Ischemia-reperfusion; Liver; NF-κB; miR-370.

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Ischemia / genetics
  • Ischemia / metabolism*
  • Liver / blood supply*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism*
  • Signal Transduction

Substances

  • MIRN370 microRNA, mouse
  • MicroRNAs
  • NF-kappa B