MicroRNA-146a Promotes Oligodendrogenesis in Stroke
Liu XS, Chopp M, Pan WL, Wang XL, Fan BY, Zhang Y, Kassis H, Zhang RL, Zhang XM, and Zhang ZG. MicroRNA-146a promotes oligodendrogenesis in stroke. Mol Neurobiol 2017; 54(1):227-237.
Stroke induces new myelinating oligodendrocytes that are involved in ischemic brain repair. Molecular mechanisms that regulate oligodendrogenesis have not been fully investigated. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression. MiR-146a has been reported to regulate immune response, but the role of miR-146a in oligodendrocyte progenitor cells (OPCs) remains unknown. Adult Wistar rats were subjected to the right middle cerebral artery occlusion (MCAo). In situ hybridization analysis with LNA probes against miR-146a revealed that stroke considerably increased miR-146a density in the corpus callosum and subventricular zone (SVZ) of the lateral ventricle of the ischemic hemisphere. In vitro, overexpression of miR-146a in neural progenitor cells (NPCs) significantly increased their differentiation into O4+ OPCs. Overexpression of miR-146a in primary OPCs increased their expression of myelin proteins, whereas attenuation of endogenous miR-146a suppressed generation of myelin proteins. MiR-146a also inversely regulated its target gene-IRAK1 expression in OPCs. Attenuation of IRAK1 in OPCs substantially increased myelin proteins and decreased OPC apoptosis. Collectively, our data suggest that miR-146a may mediate stroke-induced oligodendrogenesis.
Medical Subject Headings
Animals; Cell Differentiation; Cells, Cultured; Male; MicroRNAs; Myelin Proteins; Oligodendroglia; Rats; Rats, Wistar; Stroke