PAI-1 in tissue fibrosis.
PAI-1 in tissue fibrosis.
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DOI：
10.1002/jcp.22783
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发表时间：
2012-02
影响因子：
5.6
通讯作者：
Vaughan, Douglas E.
中科院分区：
文献类型：
--
作者：
Ghosh, Asish K.;Vaughan, Douglas E.
纤维化被定义为纤维增生性或异常成纤维细胞活化相关疾病。创面愈合的解除导致成纤维细胞的过度活化和创面区域细胞外基质（ECM）蛋白的过度积累，这是纤维化的病理表现。细胞外基质中胶原蛋白水平过高的积累取决于两个因素：胶原合成速率的增加和/或细胞蛋白水解活性对胶原蛋白降解速率的降低。尿激酶型/组织型纤溶酶原激活剂（uPA/tPA）和纤溶酶在ECM蛋白的细胞蛋白水解降解和组织稳态维持中发挥重要作用。uPA/tPA/纤溶酶和纤溶酶依赖性MMPs的活性主要依赖于uPA/tPA的有效抑制剂，纤溶酶原激活物抑制剂-1 （PAI-1）的活性。在正常生理条件下，PAI-1控制uPA/tPA/plasmin/MMP的蛋白水解活性，从而维持组织稳态。在伤口愈合过程中，PAI-1水平升高抑制uPA/tPA/纤溶酶和纤溶酶依赖性MMP活性，从而有助于加速伤口愈合。与此相反，在病理条件下，过多的PAI-1会导致胶原和其他ECM蛋白在创面过度积累，从而保留疤痕。虽然PAI-1水平在纤维化组织中显著升高，但缺乏PAI-1可以保护不同器官免受损伤相关的纤维化信号的纤维化。因此PAI-1参与不同器官的纤维化病理，包括心、肺、肾、肝和皮肤。矛盾的是，PAI-1缺乏促进自发性心脏选择性纤维化。本文就PAI-1在多器官纤维化发病机制中的意义进行综述。
Fibrosis is defined as a fibroproliferative or abnormal fibroblast activation–related disease., Deregulation of wound healing leads to hyperactivation of fibroblasts and excessive accumulation of extracellular matrix (ECM) proteins in the wound area, the pathological manifestation of fibrosis. The accumulation of excessive levels of collagen in the extracellular matrix depends on two factors: an increased rate of collagen synthesis and or decreased rate of collagen degradation by cellular proteolytic activities. The urokinase-type/tissue-type plasminogen activator (uPA/tPA) and plasmin play significant roles in the cellular proteolytic degradation of ECM proteins and the maintenance of tissue homeostasis. The activities of uPA/tPA/plasmin and plasmin-dependent MMPs rely mostly on the activity of a potent inhibitor of uPA/tPA, plasminogen activator inhibitor-1 (PAI-1). Under normal physiologic conditions, PAI-1 controls the activities of uPA/tPA/plasmin/MMP proteolytic activities and thus maintains the tissue homeostasis. During wound healing, elevated levels of PAI-1 inhibit uPA/tPA/plasmin and plasmin-dependent MMP activities and thus help expedite wound healing. In contrast to this scenario, under pathologic conditions, excessive PAI-1 contributes to excessive accumulation of collagen and other ECM protein in the wound area and thus preserves scarring. While the level of PAI-1 is significantly elevated in fibrotic tissues, lack of PAI-1 protects different organs from fibrosis in response to injury-related profibrotic signals. Thus PAI-1 is implicated in the pathology of fibrosis in different organs including the heart, lung, kidney, liver and skin. Paradoxically, PAI-1 deficiency promotes spontaneous cardiac-selective fibrosis. In this review we discuss the significance of PAI-1 in the pathogenesis of fibrosis in multiple organs.
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影响因子：
6.7
作者：
Chen, YQ;Sloan-Lancaster, J;Tseng-Crank, J
通讯作者：
Tseng-Crank, J
影响因子：
6
作者：
Chuang-Tsai, S;Sisson, TH;Simon, RH
通讯作者：
Simon, RH
影响因子：
3.1
作者：
Cesari M;Pahor M;Incalzi RA
通讯作者：
Incalzi RA
影响因子：
15.9
作者：
CARMELIET, P;STASSEN, JM;COLLEN, D
通讯作者：
COLLEN, D
DOI：
10.3969/j.issn.1672-7347.2010.10.004
发表时间：
2010-10-01
期刊：
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
影响因子：
--
作者：
Cheng, Xiaomiao;Zhou, Qiaoling;Wu, Rong
通讯作者：
Wu, Rong