Lijnen H R
Center for Molecular and Vascular Biology, KU, Leuven, Belgium.
J Thromb Haemost. 2005 Jan;3(1):35-45. doi: 10.1111/j.1538-7836.2004.00827.x.
Plasminogen activator inhibitor-1 (PAI-1), a 45-kDa serine proteinase inhibitor with reactive site peptide bond Arg345-Met346, is the main physiological plasminogen activator inhibitor. It occurs in human plasma at an antigen concentration of about 20 ng mL(-1). Besides the active inhibitory form of PAI-1 that spontaneously converts to a latent form, also a substrate form exists that is cleaved at the P1-P1' site by its target enzymes, but does not form stable complexes. Besides its role in regulating hemostasis, PAI-1 plays a role in several biological processes dependent on plasminogen activator or plasmin activity. Studies with transgenic mice have revealed a functional role for PAI-1 in wound healing, atherosclerosis, metabolic disturbances such as obesity and insulin resistance, tumor angiogenesis, chronic stress, bone remodeling, asthma, rheumatoid arthritis, fibrosis, glomerulonephritis and sepsis. It is not always clear if these functions depend on the antiproteolytic activity of PAI-1, on its binding to vitronectin or on its intereference with cellular migration or matrix binding.
纤溶酶原激活物抑制剂-1（PAI-1）是一种45 kDa的丝氨酸蛋白酶抑制剂，其反应位点肽键为Arg345-Met346，是主要的生理性纤溶酶原激活物抑制剂。它在人血浆中的抗原浓度约为20 ng/mL。除了能自发转化为潜伏形式的活性抑制形式的PAI-1外，还存在一种底物形式，该形式在P1-P1'位点被其靶酶切割，但不形成稳定的复合物。除了在调节止血中发挥作用外，PAI-1还在依赖纤溶酶原激活物或纤溶酶活性的多个生物学过程中发挥作用。对转基因小鼠的研究揭示了PAI-1在伤口愈合、动脉粥样硬化、肥胖和胰岛素抵抗等代谢紊乱、肿瘤血管生成、慢性应激、骨重塑、哮喘、类风湿性关节炎、纤维化、肾小球肾炎和败血症中的功能作用。目前尚不清楚这些功能是否取决于PAI-1的抗蛋白水解活性、其与玻连蛋白的结合或其对细胞迁移或基质结合的干扰。
