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- Title
The role of microRNA-146a in regulating the expression of IRAK1 in cerebral ischemia-reperfusion injury.
- Authors
Chu, Bo; Zhou, Yadong; Zhai, Heng; Li, Lei; Sun, Li; Li, Yun
- Abstract
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.
- Subjects
MICRORNA; ANTERIOR cerebral artery; REVERSE transcriptase polymerase chain reaction; CYTOKINES; TUMOR necrosis factors
- Publication
Canadian Journal of Physiology & Pharmacology, 2018, Vol 96, Issue 6, p611
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2017-0586