The role of microRNA-146a in regulating the expression of IRAK1 in cerebral ischemia-reperfusion injury

Can J Physiol Pharmacol. 2018 Jun;96(6):611-617. doi: 10.1139/cjpp-2017-0586. Epub 2018 Mar 5.


MicroRNA-146a (miR-146a) is reportedly implicated in the pathogenesis of ischemia-reperfusion (I/R) injury; however, its role in cerebral I/R injury is unclear and requires further investigation. In this study, cerebral I/R injury was established in mice via middle cerebral artery occlusion, and the expression of miR-146a was detected in the brain tissue via quantitative real-time PCR. We found that the expression of miR-146a was upregulated. Furthermore, the endogenous miR-146a was antagonized by its specific inhibitor. The results indicated that the inhibition of miR-146a deteriorated I/R-induced neurobehavioral impairment, exaggerated the infarct size, and exacerbated blood-brain barrier leakage. Cerebral I/R injury-induced generation of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, was further promoted by miR-146a inhibitor. The expression of interleukin-1 receptor associated kinase 1 (IRAK1), a target of miR-146a, was upregulated upon miR-146a inhibition. In addition, the nuclear factor κB (NF-κB) signaling pathway was over-activated when miR-146a was antagonized as manifested by the increased levels of phospho-NF-κB inhibitor α and nuclear p65. In summary, our findings demonstrate that the elevation of miR-146a may be one of the compensatory responses after the cerebral I/R injury and suggest miR-146a as a potential therapeutic target for cerebral I/R injury.

Keywords: IRAK1; NF-κB; cerebral I/R injury; inflammatory response; lésions d’I/R cérébrales; miR-146a; réaction inflammatoire.

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / complications*
  • Gene Expression Regulation, Enzymologic / genetics*
  • Gene Knockdown Techniques
  • Interleukin-1 Receptor-Associated Kinases / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • Reperfusion Injury / complications
  • Reperfusion Injury / enzymology*
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology
  • Signal Transduction / genetics


  • MicroRNAs
  • Mirn146 microRNA, mouse
  • NF-kappa B
  • Interleukin-1 Receptor-Associated Kinases