Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis.

Enzyme & protein Pub Date : 1996-01-01 DOI:10.1159/000468622
M S Pepper, R Montesano, S J Mandriota, L Orci, J D Vassalli
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引用次数: 225

Abstract

Extracellular proteolysis is required for matrix degradation and the regulation of cytokine activity during angiogenesis, and this is dependent on a cohort of proteases and protease inhibitors produced by endothelial and nonendothelial cells. The plasminogen activator (PA)/plasmin system has been extensively investigated in these processes, and descriptive studies have demonstrated that urokinase-type PA (uPA), uPA receptor (uPAR) and PA inhibitor-1 (PAI-1) are expressed by endothelial cells during angiogenesis in vivo. In vitro studies have led to the notion that normal capillary morphogenesis is dependent on a protease-antiprotease equilibrium. These findings are discussed in the context of recent observations on uPA-, uPAR-, PAI-1 and plaminogen-deficient mice, in which developmental and physiological angiogenesis appear to occur normally. This has led to a reevaluation of the role of the PA/plasmin system during angiogenesis. In particular, these observations raise the possibility that the role of this system may be limited to situations in which endothelial cells encounter and must degrade fibrin in order to form new capillary sprouts.

血管生成:在细胞迁移和形态发生过程中平衡的细胞外蛋白水解的范例。
细胞外蛋白水解是血管生成过程中基质降解和细胞因子活性调节所必需的,这依赖于内皮细胞和非内皮细胞产生的一系列蛋白酶和蛋白酶抑制剂。在这些过程中,纤溶酶原激活物(PA)/纤溶酶系统被广泛研究,描述性研究表明,尿激酶型PA (uPA)、uPA受体(uPAR)和PA抑制剂-1 (PAI-1)在体内血管生成过程中由内皮细胞表达。体外研究表明,正常的毛细血管形态形成依赖于蛋白酶-抗蛋白酶平衡。这些发现在最近对uPA-、uPAR-、PAI-1和血小板原缺乏小鼠的观察中进行了讨论,在这些小鼠中,发育和生理性血管生成似乎正常发生。这导致了对PA/纤溶酶系统在血管生成过程中的作用的重新评估。特别是,这些观察结果提出了这样一种可能性,即该系统的作用可能仅限于内皮细胞遇到并必须降解纤维蛋白以形成新的毛细血管芽的情况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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