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dc.contributor.authorSabirzhanov, B.
dc.contributor.authorFaden, A.I.
dc.contributor.authorWu, J.
dc.date.accessioned2019-11-20T15:51:41Z
dc.date.available2019-11-20T15:51:41Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85074550822&doi=10.1038%2fs41419-019-2079-y&partnerID=40&md5=50110e8097d112351fa54368335426ef
dc.identifier.urihttp://hdl.handle.net/10713/11415
dc.description.abstractSpinal cord injury (SCI) causes neuronal cell death and vascular damage, which contribute to neurological dysfunction. Given that many biochemical changes contribute to such secondary injury, treatment approaches have increasingly focused on combined therapies or use of multi-functional drugs. MicroRNAs (miRs) are small (20-23 nucleotide), non-protein-coding RNAs and can negatively regulate target gene expression at the post-transcriptional level. As individual miRs can potentially modulate expression of multiple relevant proteins after injury, they are attractive candidates as upstream regulators of the secondary SCI progression. In the present study we examined the role of miR-711 modulation after SCI. Levels of miR-711 were increased in injured spinal cord early after SCI, accompanied by rapid downregulation of its target angiopoietin-1 (Ang-1), an endothelial growth factor. Changes of miR-711 were also associated with downregulation of the pro-survival protein Akt (protein kinase B), another target of miR-711, with sequential activation of glycogen synthase kinase 3 and the pro-apoptotic BH3-only molecule PUMA. Central administration of a miR-711 hairpin inhibitor after SCI limited decreases of Ang-1/Akt expression and attenuated apoptotic pathways. Such treatment also reduced neuronal/axonal damage, protected microvasculature and improved motor dysfunction following SCI. In vitro, miR-711 levels were rapidly elevated by neuronal insults, but not by activated microglia and astrocytes. Together, our data suggest that post-traumatic miR-711 elevation contributes to neuronal cell death after SCI, in part by inhibiting Ang-1 and Akt pathways, and may serve as a novel therapeutic target. Copyright 2019, The Author(s).en_US
dc.description.sponsorshipThe work was supported by the National Institutes of Health Grants R01 NS094527 (J.W.), 2R01 NR013601 (J.W./A.I.F.), R01 NS110635 (J.W./A.I.F.), R01 NS110567 (J.W.), RF1 NS110637 (J.W.), R01 NS096002 (B.A.S./B.S.), and Craig H. Nielson Foundation Research (340442) (A.I.F.).en_US
dc.description.urihttps://doi.org/10.1038/s41419-019-2079-yen_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofCell Death and Disease
dc.subject.meshCell Deathen_US
dc.subject.meshNervous Systemen_US
dc.subject.meshTrauma, Nervous Systemen_US
dc.subject.meshMicroRNAsen_US
dc.titleInhibition of microRNA-711 limits angiopoietin-1 and Akt changes, tissue damage, and motor dysfunction after contusive spinal cord injury in miceen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41419-019-2079-y
dc.identifier.pmid31685802


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