Acevedo Lisette, Yu Jun, Erdjument-Bromage Hediye, Miao Robert Qing, Kim Ji-Eun, Fulton David, Tempst Paul, Strittmatter Stephen M, Sessa William C
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.
Nat Med. 2004 Apr;10(4):382-8. doi: 10.1038/nm1020. Epub 2004 Mar 21.
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.
尽管Nogo-A在中枢神经系统中已被确定为轴突再生的抑制剂，但Nogo异构体在周围组织中的作用几乎仍不为人知。在此，我们通过蛋白质组学分析来鉴定富含小窝和/或脂筏（CEM/LR）的蛋白质，结果表明Nogo-B在培养的内皮细胞和平滑肌细胞以及完整血管中高表达。Nogo-B的N末端促进内皮细胞迁移，但抑制血管平滑肌（VSM）细胞迁移，而这些过程是血管重塑所必需的。Nogo-A/B缺陷小鼠的血管损伤会促进过度的内膜增生，腺病毒介导的Nogo-B基因转移可挽救这些基因敲除小鼠的异常血管扩张。我们发现Nogo-B是血管稳态和重塑的调节因子，这拓宽了该蛋白家族的功能范围。
