MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway

Biosci Biotechnol Biochem. 2019 May;83(5):829-835. doi: 10.1080/09168451.2019.1569495. Epub 2019 Jan 27.

Abstract

MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups. The protein expression of TNF receptor-associated factor 6 (TRAF6), IL-1β and the phosphorylation of p65 (p-p65) were suppressed by the up-regulation of miR-125b. Furthermore, the nuclear translocation of p-p65, measured by immunofluorescence, was enhanced by the miR-125b inhibitors. In conclusion, our study indicates that miR-125b protects liver from hepatic I/R injury via inhibiting TRAF6 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway.

Keywords: Mir-125b; NF-κB; TRAF6; hepatic ischemia/reperfusion.

MeSH terms

  • Animals
  • Cytokines / genetics
  • Inflammation Mediators / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Liver / blood supply*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / physiology*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • RAW 264.7 Cells
  • Reperfusion Injury / metabolism*
  • Signal Transduction / genetics
  • TNF Receptor-Associated Factor 6 / metabolism*

Substances

  • Cytokines
  • Inflammation Mediators
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • Mirn125 microRNA, mouse
  • NF-kappa B
  • TNF Receptor-Associated Factor 6
  • Tifab protein, human