Biological and clinical aspects of plasminogen activator inhibitor type 2.

نویسندگان

  • E K Kruithof
  • M S Baker
  • C L Bunn
چکیده

T HE PLASMINOGEN activator (PA) system is responsible for the degradation of intravascular blood clots,’ while also contributing to extracellular proteolysis in a wide variety of physiological (eg, tissue remodeling, cell migration, wound healing, angiogenesis, trophoblast implantation, ovulation, and fetal development) and pathological (eg, acute and chronic inflammation, preeclampsia, intrauterine growth retardation, tumor invasion, and metastasis) processes.24 Rapid progress in the understanding of the role of the PA system in these processes has been obtained recently by studying transgenic mice deficient in t-PA, U-PA, plasminogen activator inhibitor-l (PAI-1) or combined t-PNu-PA.’ These studies have confirmed the significant role of the PA system in fibrin clot surveillance, wound healing, tissue remodelling, and arterial neointima formation and seems to be required for normal health and survival. Plasmin, a trypsin-like protease, is generated from its precursor plasminogen by the action of plasminogen activators (PA) of which there are two types, tissue-type PA (t-PA) and urokinase (U-PA). Plasmin degrades fibrin and several extracellular matrix and adhesion proteins (eg, proteoglycans, laminin, fibronectin, vitronectin) and, by activation of procollagenases, may contribute to collagen degradation. To avoid excessive proteolysis and tissue damage, a precise, coordinated, spatial, and temporal regulation of the PA system is required. This is achieved through the interaction of an astounding variety of regulatory mechanisms including: (1) inhibition by specific plasminand PA-inhibitors; (2) binding of plasminogen, PAS and their inhibitors to fibrin, extracellular matrix proteins, and specific cell surface receptors, thereby regulating the rate of plasminogen activation and modifying the efficacy of the inhibitors; (3) release of t-PA and PAI-1 from intracellular storage granules; (4) regulation of gene expression of PAS and PAIs by hormones, growth factors, and cytokines; (5) an autocrine feedback loop whereby plasmin-mediated activation of latent forms of growth factors regulates the expression of PAS and PAIS; and (6) clearance of free and PAI-bound PAS via specific receptors.’.’’ The principal PA-inhibitors are PAI-1 and PAI-2. The aim of the present review is to bring together recent findings concerning the properties of PAL2 (Table l), its gene structure, its cellular distribution, the regulation of its gene expression, and its potential role in pregnancy, skin, inflammation, wound healing, tumor invasion, and metastasis.

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عنوان ژورنال:
  • Blood

دوره 86 11  شماره 

صفحات  -

تاریخ انتشار 1995