A new role for Nogo as a regulator of vascular remodeling.
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.
Acevedo
Lisette
L
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.
Yu
Jun
J
Erdjument-Bromage
Hediye
H
Miao
Robert Qing
RQ
Kim
Ji-Eun
JE
Fulton
David
D
Tempst
Paul
P
Strittmatter
Stephen M
SM
Sessa
William C
WC
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
D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse