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dc.contributor.authorWälchli, Thomas
dc.contributor.authorPernet, Vincent
dc.contributor.authorWeinmann, Oliver
dc.contributor.authorShiu, Jau-Ye
dc.contributor.authorGuzik-Kornacka, Anna
dc.contributor.authorDecrey, Guillaume
dc.contributor.authorYüksel, Deniz
dc.contributor.authorSchneider, Hannah
dc.contributor.authorVogel, Johannes
dc.contributor.authorIngber, Donald
dc.contributor.authorVogel, Viola
dc.contributor.authorFrei, Karl
dc.contributor.authorSchwab, Martin
dc.date.accessioned2019-10-03T14:38:04Z
dc.date.issued2013
dc.identifier.citationWalchli, T., V. Pernet, O. Weinmann, J.-Y. Shiu, A. Guzik-Kornacka, G. Decrey, D. Yuksel, et al. 2013. “Nogo-A Is a Negative Regulator of CNS Angiogenesis.” Proceedings of the National Academy of Sciences 110 (21): E1943–52. https://doi.org/10.1073/pnas.1216203110.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41461172*
dc.description.abstractNogo-A is an important axonal growth inhibitor in the adult and developing CNS. In vitro, Nogo-A has been shown to inhibit migration and cell spreading of neuronal and nonneuronal cell types. Here, we studied in vivo and in vitro effects of Nogo-A on vascular endothelial cells during angiogenesis of the early postnatal brain and retina in which Nogo-A is expressed by many types of neurons. Genetic ablation or virus-mediated knock down of Nogo-A or neutralization of Nogo-A with an antibody caused a marked increase in the blood vessel density in vivo. In culture, Nogo-A inhibited spreading, migration, and sprouting of primary brain microvascular endothelial cells (MVECs) in a dose-dependent manner and induced the retraction of MVEC lamellipodia and filopodia. Mechanistically, we show that only the Nogo-A-specific Delta 20 domain exerts inhibitory effects on MVECs, but the Nogo-66 fragment, an inhibitory domain common to Nogo-A, -B, and -C, does not. Furthermore, the action of Nogo-A Delta 20 on MVECs required the intracellular activation of the Ras homolog gene family, member A (Rho-A)associated, coiled-coil containing protein kinase (ROCK)-Myosin II pathway. The inhibitory effects of early postnatal brain membranes or cultured neurons on MVECs were relieved significantly by anti-Nogo- A antibodies. These findings identify Nogo-A as an important negative regulator of developmental angiogenesis in the CNS. They may have important implications in CNS pathologies involving angiogenesis such as stroke, brain tumors, and retinopathies.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleNogo-A is a negative regulator of CNS angiogenesis
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorIngber, Donald Elliot::577cf2edd94eeff15bcf7e5951504981::600
dc.date.available2019-10-03T14:38:04Z
dash.workflow.comments1Science Serial ID 91069
dc.identifier.doi10.1073/pnas.1216203110
dash.source.volume110;21
dash.source.pageE1943


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