Castellino Francis J, Ploplis Victoria A
W.M Keck Center for Transgene Research, Department of Chemistry and Biochemistry, University of Notre Dame, IN 46556, USA.
Thromb Haemost. 2005 Apr;93(4):647-54. doi: 10.1160/TH04-12-0842.
Activation of the fibrinolytic system is dependent on the conversion of the plasma zymogen, plasminogen (Pg), to the serine protease plasmin (Pm) by the physiological activators urokinase-type Pg activator (uPA) or tissue-type plasminogen activator (tPA). The primary in vivo function of Pm is to regulate vascular patency by degrading fibrin-containing thrombi. However, the identification of Pg/Pm receptors and the ability of Pm to degrade other matrix proteins have implicated Pm in other functions involving degradation of protein barriers, thereby mediating cell migration, an important event in a number of normal e.g., embryogenesis, wound healing, angiogenesis, and pathological, e.g., tumor growth and dissemination, processes. Prior to the development of Pg-deficient mice, much of the evidence for its role in other biological events was based on indirect studies. With the development and characterization of these mice, and ability to apply challenges utilizing a number of animal models that mimic the human condition, a clearer delineation of Pg/Pm function has evolved and has contributed to an understanding of mechanisms associated with a number of pathophysiological events.
纤溶系统的激活依赖于生理性激活剂尿激酶型纤溶酶原激活剂（uPA）或组织型纤溶酶原激活剂（tPA）将血浆中的酶原纤溶酶原（Pg）转化为丝氨酸蛋白酶纤溶酶（Pm）。Pm在体内的主要功能是通过降解含纤维蛋白的血栓来调节血管通畅。然而，Pg/Pm受体的鉴定以及Pm降解其他基质蛋白的能力表明，Pm参与了其他涉及蛋白屏障降解的功能，从而介导细胞迁移，这是许多正常过程（如胚胎发育、伤口愈合、血管生成）和病理过程（如肿瘤生长和扩散）中的一个重要事件。在缺乏Pg的小鼠模型建立之前，关于其在其他生物学事件中作用的许多证据都基于间接研究。随着这些小鼠模型的建立和特征描述，以及利用多种模拟人类疾病状况的动物模型进行挑战的能力，对Pg/Pm功能有了更清晰的界定，并有助于理解与许多病理生理事件相关的机制。
