miR-155 Knockdown Protects against Cerebral Ischemia and Reperfusion Injury by Targeting MafB.

BACKGROUND:Studies have elucidated that the variable expression levels of miRNAs influence the inflammatory process in ischemic stroke. Nevertheless, the impact and potential mechanism of miR-155 in cerebral ischemia-reperfusion injury (CIRI) keep to be incompletely known. METHODS:The levels of miR-155 and MafB were determined via qRT-PCR, western blot, or immunohistochemistry assays in plasma of patients with CIRI, oxygen glucose deprivation/reoxygenation (OGD/R) induced SH-SY5Y cells, and mouse models with middle cerebral artery occlusion (MCAO). The association between miR-155 and MafB was validated via dual-luciferase reporter and western blot assays. Cell viability, apoptosis, invasion, and migration were evaluated through MTT, flow cytometry, Transwell and wound healing assays. Infarction volume was measured in MCAO mouse brain tissues by TTC assay. The expression of inflammatory mediators was measured by ELISA in cells and brain tissues. RESULTS:miR-155 level was upregulated whereas MafB was downregulated in the plasma of patients with CIRI, OGD/R-induced SH-SY5Y cells, also as mouse models with MCAO injury. Mechanistically, miR-155 directly targeted 3'UTR of MafB and restrained MafB expression in OGD/R injury SH-SY5Y cells. Downregulation of miR-155 attenuated OGD/R-induced injury through increasing proliferation, inhibiting apoptosis, enhancing invasion and migration abilities, and constraining the expression of inflammatory mediators (IL-1β, IL-6, and TNF-α) and inflammatory enzymes (iNOS and COX-2) in SH-SY5Y cells following OGD/R, while MafB inhibition reversed the protective effects. In vivo, downregulating miR-155 reduced the infarction volume in the MACO mouse brain. Furthermore, miR-155 knockdown inhibited the IL-1β, IL-6, and TNF-α) and inflammatory enzymes (iNOS and COX-2) in SH-SY5Y cells following OGD/R, while MafB inhibition reversed the protective effects. CONCLUSION:Our results suggest that miR-155 knockdown alleviated ischemia-reperfusion injury by targeting MafB to improve the neurological function and inhibit inflammation response, highlighting a novel therapeutic strategist for CIRI.

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