VASCULAR ENDOTHELIAL GROWTH-FACTOR INCREASES UROKINASE RECEPTOR EXPRESSION IN VASCULAR ENDOTHELIAL-CELLS
VASCULAR ENDOTHELIAL GROWTH-FACTOR INCREASES UROKINASE RECEPTOR EXPRESSION IN VASCULAR ENDOTHELIAL-CELLS
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DOI：
10.1074/jbc.270.17.9709
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发表时间：
1995-04-28
影响因子：
4.8
通讯作者：
PEPPER, MS
中科院分区：
文献类型：
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作者：
MANDRIOTA, SJ;SEGHEZZI, G;PEPPER, MS
血管内皮生长因子(VEGF)是一种强大的血管生成因子和内皮细胞特异性的丝裂原，能刺激血管内皮细胞的尿激酶型纤溶酶原激活物(UPA)活性。在这里，我们报告了VEGP增加了uPA与相同细胞的高亲和力结合，并且这种结合被与uPA的uPA受体(UPAR)结合生长因子样域相对应的肽所阻止。配体交联、配体印迹和uPA-Sephose亲和层析显示，细胞表面uPA结合蛋白增加，与uPAR相对应，基于其对uPA的亲和力，M(R)为50,000-55,000，以及磷脂酰肌醇特异性磷脂酶C的敏感性。经Scatchard分析，VEGF使uPAR分子数量增加2.83.5倍，同时通过Northern印迹法降低其与uPA的亲和力。综上所述，这些发现表明，血管生成伴随着内皮细胞表面uPAR表达和uPA活性的增加。这些观察结果与uPA-uPAR相互作用促进细胞入侵的观点是一致的。
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and endothelial cell-specific mitogen that stimulates urokinase-type plasminogen activator (uPA) activity in vascular endothelial cells. Here, we report that VEGP increases the high affinity binding of uPA to the same cells and that this binding is prevented by a peptide corresponding to the uPA receptor (uPAR) binding growth factor-like domain of uPA. Ligand crosslinking, ligand blotting, and uPA-Sepharose affinity chromatography revealed an increase in a cell surface uPA binding protein that corresponds to the uPAR on the basis of its affinity for uPA, M(r) of 50,000-55,000, and phosphatidylinositol-specific phospholipase C sensitivity. By Scatchard analysis, VEGF increased the number of uPAR molecules by 2.83.5 fold and concomitantly decreased their affinity for uPA By northern blotting uPAR mRNA was increased in a dose- and time dependent manner in response to VEGF. Taken together, these findings demonstrate that VEGF-induced angiogenesis is accompanied by increased uPAR expression and uPA activity on the endothelial cell surface. These observations are consistent with the notion that the uPA-uPAR interaction facilitates cellular invasion.