Matthies Annette M, Low Quentin E H, Lingen Mark W, DiPietro Luisa A
Burn and Shock Trauma Institute and the Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Am J Pathol. 2002 Jan;160(1):289-96. doi: 10.1016/S0002-9440(10)64372-6.
Angiogenesis, the formation of new capillaries from existing vasculature, plays an essential role in tissue repair. The rapid onset and predominance of proangiogenic factors optimizes healing in damaged tissues. One factor that directly mediates wound vessel angiogenesis is vascular endothelial growth factor (VEGF). Although much is known about the biology of VEGF and its cognate receptors, VEGFR1 and VEGFR2, the role of a recently identified co-receptor for VEGF, neuropilin-1, is not well understood. Using a murine model of dermal wound repair, we found that neuropilin-1 was abundantly expressed on new vasculature in healing wounds. Moreover, mice treated with anti-neuropilin-1 antibodies exhibited a significant decrease in vascular density within these wounds (67% decrease, P = 0.0132). In in vitro assays, VEGF induced formation of endothelial cord-like structures on collagen gel and endothelial cell migration toward VEGF was inhibited by antibodies directed against neuropilin-1. These results provide both in vitro and in vivo evidence for a critical role of neuropilin-1 in wound angiogenesis.
血管生成,即从现有脉管系统形成新的毛细血管,在组织修复中起着至关重要的作用。促血管生成因子的快速出现和主导作用优化了受损组织的愈合。直接介导伤口血管生成的一个因子是血管内皮生长因子(VEGF)。尽管对VEGF及其同源受体VEGFR1和VEGFR2的生物学特性已了解很多,但最近发现的VEGF共受体神经纤毛蛋白-1的作用尚未得到充分理解。利用小鼠皮肤伤口修复模型,我们发现神经纤毛蛋白-1在愈合伤口的新脉管系统上大量表达。此外,用抗神经纤毛蛋白-1抗体处理的小鼠在这些伤口内的血管密度显著降低(降低67%,P = 0.0132)。在体外试验中,VEGF诱导胶原凝胶上形成内皮索状结构,而针对神经纤毛蛋白-1的抗体抑制内皮细胞向VEGF的迁移。这些结果为神经纤毛蛋白-1在伤口血管生成中的关键作用提供了体外和体内证据。