Binder Bernd R, Mihaly Judit, Prager Gerald W
Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
Thromb Haemost. 2007 Mar;97(3):336-42.
The urokinase-type plasminogen activator (uPA), its inhibitor PAI-1 and its cellular receptor (uPAR), play a pivotal role in pericellular proteolysis. In addition, through their interactions with extracellular matrix proteins as well as with transmembrane receptors and other links to the intracellular signaling machinery, they modulate cell migration, cell-matrix interactions and signaling pathways. A large body of experimental evidence from in-vitro and in-vivo data as well as from the clinics indicates an important role of the uPA-uPAR-PAI-1 systems in cancer. In addition to their role in tumor cell biology, the uPA-uPAR-PAI-1 systems are also important for vascular biology by modulating angiogenesis and by altering migration of smooth muscle cells and fibrin deposition in atherosclerosis and restenosis. This review will focus on the general mechanism of uPAR/uPA/PAI-1 interactions and signaling and the possible relevance of this system in vascular biology.
尿激酶型纤溶酶原激活物（uPA）、其抑制剂PAI-1及其细胞受体（uPAR）在细胞周围蛋白水解过程中起关键作用。此外，通过它们与细胞外基质蛋白的相互作用以及与跨膜受体的相互作用以及与细胞内信号传导机制的其他联系，它们调节细胞迁移、细胞-基质相互作用和信号通路。来自体外和体内数据以及临床的大量实验证据表明uPA-uPAR-PAI-1系统在癌症中起重要作用。除了它们在肿瘤细胞生物学中的作用外，uPA-uPAR-PAI-1系统通过调节血管生成以及改变平滑肌细胞迁移和动脉粥样硬化及再狭窄中的纤维蛋白沉积，对血管生物学也很重要。本综述将重点关注uPAR/uPA/PAI-1相互作用和信号传导的一般机制以及该系统在血管生物学中的可能相关性。
