title: A new role for Nogo as a regulator of vascular remodeling.
abstract: Although Nogo-A has been identified in the central nervous system as an inhibitor of axonal regeneration, the peripheral roles of Nogo isoforms remain virtually unknown. Here, using a proteomic analysis to identify proteins enriched in caveolae and/or lipid rafts (CEM/LR), we show that Nogo-B is highly expressed in cultured endothelial and smooth muscle cells, as well as in intact blood vessels. The N terminus of Nogo-B promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle (VSM) cells, processes necessary for vascular remodeling. Vascular injury in Nogo-A/B-deficient mice promotes exaggerated neointimal proliferation, and adenoviral-mediated gene transfer of Nogo-B rescues the abnormal vascular expansion in those knockout mice. Our discovery that Nogo-B is a regulator of vascular homeostasis and remodeling broadens the functional scope of this family of proteins.
authors.affiliation: Department of Pharmacology and Program in Vascular Cell Signaling and Therapeutics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors.forename: Lisette
authors.initials: L
authors.lastname: Acevedo
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Robert Qing
authors.initials: RQ
authors.lastname: Miao
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Fulton
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009185:Myelin Proteins / Q000378:metabolism / Q000502:physiology*; D000070798:Nogo Proteins; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse