• Arch Med Sci · Jun 2018

    MicroRNA-135b-5p prevents oxygen-glucose deprivation and reoxygenation-induced neuronal injury through regulation of the GSK-3β/Nrf2/ARE signaling pathway.

    • Qiang Duan, Wei Sun, Hua Yuan, and Xiang Mu.
    • Department of Rehabilitation Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
    • Arch Med Sci. 2018 Jun 1; 14 (4): 735-744.

    IntroductionMicroRNAs (miRNAs) are emerging as critical regulators in the pathological process of cerebral ischemia/reperfusion injury. miRNAs play an important role in regulating neuronal survival. miR-135b-5p has been reported as an important miRNA in regulating cell apoptosis. However, the role of miR-135b-5p in regulating neuronal survival remains poorly understood. Here, we aimed to investigate the role of miR-135b-5p in cerebral ischemia/ reperfusion using an in vitro model of oxygen-glucose deprivation and reoxygenation-(OGD/R) induced neuron injury.Material And MethodsmiRNA, mRNA and protein expression was detected by real-time quantitative polymerase chain reaction and Western blot. Cell viability was detected by cell counting kit-8 and lactate dehydrogenase assays. Cell apoptosis was detected by caspase-3 activity assay. Oxidative stress was determined using commercial kits. The target of miR-135b-5p was confirmed by dual-luciferase reporter assay.ResultsWe found that miR-135b-5p expression was significantly decreased in hippocampal neurons receiving OGD/R treatment. Overexpression of miR-135b-5p markedly alleviated OGD/R-induced cell injury and oxidative stress, whereas suppression of miR-135b-5p showed the opposite effects. We observed that miR-135b-5p directly targeted the 3'-untranslated region of glycogen synthase kinase-3β (GSK-3β). We found that miR-135b-5p negatively regulates the expression of GSK-3β in hippocampal neurons. Moreover, miR-135b-5p overexpression promotes activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling. However, the restoration of GSK-3β expression significantly reversed the protective effects of miR-135b-5p overexpression.ConclusionsOverall, our results suggest that miR-135b-5p protects neurons against OGD/R-induced injury through downregulation of GSK-3β and promotion of the Nrf2/ARE signaling pathway-mediated antioxidant responses.

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