title: MicroRNA-146a Promotes Oligodendrogenesis in Stroke.
abstract: 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.
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA. xsliu@neuro.hfh.edu.
authors.forename: Xian Shuang
authors.initials: XS
authors.lastname: Liu
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.|Department of Physics, Oakland University, Rochester, MI, 48309, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.|Medical Imaging Institute of North Sichuan Medical University, Nanchong, Sichuan, China, 637100.
authors.forename: Wan Long
authors.initials: WL
authors.lastname: Pan
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.
authors.forename: Xin Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.
authors.forename: Bao Yan
authors.initials: BY
authors.lastname: Fan
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Kassis
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.affiliation: Medical Imaging Institute of North Sichuan Medical University, Nanchong, Sichuan, China, 637100.
authors.forename: Xiao Ming
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, MI, 48202, USA.
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D009185:Myelin Proteins / Q000096:biosynthesis; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control
chemical_list: C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D009185:Myelin Proteins
keywords: Differentiation; IRAK1; Oligodendrocyte progenitor cells; Stroke; Survival; miR-146a