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dc.contributor.authorLi, Longxuan
dc.contributor.authorWelser-Alves, Jennifer
dc.contributor.authorvan der Flier, Arjan
dc.contributor.authorBoroujerdi, Amin
dc.contributor.authorMilner, Richard
dc.contributor.authorHynes, Richard O
dc.date.accessioned2016-02-25T16:10:43Z
dc.date.available2016-02-25T16:10:43Z
dc.date.issued2012-06
dc.date.submitted2012-06
dc.identifier.issn00144886
dc.identifier.issn1090-2430
dc.identifier.urihttp://hdl.handle.net/1721.1/101277
dc.description.abstractFibronectin is a critical regulator of vascular modelling, both in development and in the adult. In the hypoxic adult central nervous system (CNS), fibronectin is induced on angiogenic vessels, and endothelial cells show strong induction of the two fibronectin receptors α5β1 and αvβ3 integrins. In a previous study, we found that the αvβ3 integrin is dispensable for hypoxic-induced cerebral angiogenesis, but a role for the endothelial α5β1 integrin was suggested. To directly investigate the role of endothelial α5 integrin in cerebral angiogenesis, wild-type mice and mice lacking α5 integrin expression in endothelial cells (α5-EC-KO) were subject to hypoxia (8% O[subscript 2]) for 0, 2, 4, 7 or 14 days. Quantification of cerebral vessel density and endothelial-specific proteins claudin-5 and Glut-1 revealed that α5-EC-KO mice displayed an attenuated angiogenic response, which correlated with delayed endothelial proliferation. α5-EC-KO mice showed no defect in the ability to organize a cerebrovascular fibronectin matrix, and no compensatory increase in vascular αvβ3 integrin expression. Consistent with these findings, primary α5KO brain endothelial cells (BEC) in culture exhibited delayed growth and proliferation. Taken together, these studies demonstrate an important angiogenic role for the α5β1 integrin in promoting BEC proliferation in response to cerebral hypoxia.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (PO1-HL66105)en_US
dc.description.sponsorshipNational Institute of General Medical Sciences (U.S.). Cell Migration Consortium (GC11451.126452)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.expneurol.2012.06.005en_US
dc.rightsCreative Commons Attribution-Noncommercial-NoDerivativesen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleAn angiogenic role for the α5β1 integrin in promoting endothelial cell proliferation during cerebral hypoxiaen_US
dc.typeArticleen_US
dc.identifier.citationLi, Longxuan, Jennifer Welser-Alves, Arjan van der Flier, Amin Boroujerdi, Richard O. Hynes, and Richard Milner. “An Angiogenic Role for the Α5β1 Integrin in Promoting Endothelial Cell Proliferation During Cerebral Hypoxia.” Experimental Neurology 237, no. 1 (September 2012): 46–54.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorvan der Flier, Arjanen_US
dc.contributor.mitauthorHynes, Richard O.en_US
dc.relation.journalExperimental Neurologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLi, Longxuan; Welser-Alves, Jennifer; van der Flier, Arjan; Boroujerdi, Amin; Hynes, Richard O.; Milner, Richarden_US
dc.identifier.orcidhttps://orcid.org/0000-0001-7603-8396
mit.licensePUBLISHER_CCen_US


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