Volpert O, Jackson D, Bouck N, Linzer D I
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA. Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Endocrinology. 1996 Sep;137(9):3871-6. doi: 10.1210/endo.137.9.8756559.
Proliferin stimulates endothelial cell migration in culture and neovascularization in vivo. Previous studies have demonstrated that proliferin can bind to the insulin-like growth factor II/mannose 6-phosphate receptor, and that binding can be blocked by mannose 6-phosphate. We have now found that this receptor plays an essential role in proliferin-induced angiogenesis. Proliferin binding to endothelial cells is blocked by the addition of mannose 6-phosphate, as is the ability of both recombinant and placental-derived proliferin to stimulate the migration of capillary endothelial cells in vitro and to induce neovascularization in the rat cornea. Consistent with a direct role of this receptor in angiogenesis, insulin-like growth factor II, as well as a mutant form of insulin-like growth factor II that binds to the insulin-like growth factor II/mannose 6-phosphate receptor but not to the insulin-like growth factor I receptor, also stimulate endothelial cell migration and neovascularization.
增殖蛋白可刺激培养中的内皮细胞迁移以及体内血管新生。先前的研究表明，增殖蛋白能与胰岛素样生长因子II/甘露糖6-磷酸受体结合，且这种结合可被甘露糖6-磷酸阻断。我们现已发现，该受体在增殖蛋白诱导的血管生成中起关键作用。添加甘露糖6-磷酸可阻断增殖蛋白与内皮细胞的结合，重组增殖蛋白和胎盘衍生的增殖蛋白在体外刺激毛细血管内皮细胞迁移以及在大鼠角膜诱导血管新生的能力也会被阻断。与该受体在血管生成中的直接作用一致，胰岛素样生长因子II以及一种与胰岛素样生长因子II/甘露糖6-磷酸受体结合但不与胰岛素样生长因子I受体结合的胰岛素样生长因子II突变体，也能刺激内皮细胞迁移和血管新生。
