MicroRNA-29a-5p Attenuates Oxygen-glucose Deprivation and Reoxygenation Injury in Astrocytes by Targeting Glycogen Synthase Kinase beta

Background: Cerebral ischemia-reperfusion injury (CIRI) after endovascular reperfusion treatment is associated with adverse prognosis in acute ischemic stroke patients. MicroRNAs contribute to CIRI and become the diagnostic and prognosis biomarkers for acute ischemic stroke. In this study, we investigate the role of microRNA-29a-5p in CIRI in the oxygen-glucose deprivation and reoxygenation (OGD/R) model of neurovascular cells. Methods: The expression of microRNA-29a-5p in rat neurons, astrocytes, brain microvascular endothelial cells, microglia, and pericytes model of OGD/R were assessed. The astrocyte injury, phenotype shifting of reactive astrocytes, and regulation of microRNA-29a-5p target genes were evaluated after microRNA-29a-5p mimics and inhibitors treatment in the OGD/R model. Results: MicroRNA-29a-5p decreased in the astrocyte model 24 hours after OGD/R but did not significantly change in the other neurovascular cells after OGD/R. Twelve predicted target genes for microRNA-29a-5p were significantly differentially expressed in the astrocyte OGD/R model; eleven participated in the Wnt signaling pathway. Increased microRNA-29a-5p alleviated astrocyte injury and cell apoptosis. Overexpression of microRNA-29a-5p suppressed neurotoxic A1 astrocyte markers of complement 3, FK506 binding protein 51, and Serping1 and increased neuroprotective A2 astrocyte markers of S100a10, Pentraxin 3, and Emp1. MicroRNA-29a-5p effectively regulated the direct target gene of Glycogen synthase kinase (GSK)-3beta expression and its downstream beta-catenin in astrocytes after OGD/R. Conclusions: MicroRNA-29a-5p alleviated astrocyte injury, transformed the A1/A2 phenotype of reactive astrocyte, and regulated its direct target gene of GSK-3beta and its downstream mediator of beta-catenin in astrocytes after OGD/R. Astrocytic microRNA-29a-5p may be a protective target for reducing CIRI. ### Competing Interest Statement The authors have declared no competing interest.