CONTROL OF FIBRIN TURNOVER IN PLEURAL DISEASE

临床和实验观察表明，血管外纤维蛋白 沉积在胸膜组织的发病机制中起重要作用。 然而，对局部纤维蛋白周转的控制知之甚少。 在急性胸膜损伤和纤维化修复过程中。我们将使用 兔胸膜损伤模型的建立及其体内机制的研究 对纤维蛋白的形成和纤溶的影响 到突起的间皮。体外互补实验 将被用来定义纤维蛋白周转的途径，通过这些途径 细胞通过控制凝血和调节影响重塑 尿激酶及其受体(UPAR)对蛋白质的分解作用。我们还将 确定uPAR对间皮细胞功能的影响，包括 增殖和迁移并阐明调节uPAR的机制 表情。我们将运用多种蛋白质化学、分子生物学 和免疫组织学技术来解决这些目标。组织 损伤后的胸膜间隔会导致局部瘢痕形成， 与肺功能受限和侵袭性有关的发病率 治疗程序。我们的假设是胸膜组织和 选择性干扰局部纤维蛋白可防止瘢痕形成 队形和/或净空。我们的研究将确定这些因素的作用 胸膜组织中的途径，并可能提供新的临床 抢占或限制这一进程的策略。

Clinical and experimental observations indicate that extravascular fibrin deposition is important in the pathogenesis of pleural organization. However, little is known about the control of local fibrin turnover during evolving acute pleural injury and fibrotic repair. We will use an established rabbit model of pleural injury to identify in vivo mechanisms of fibrin formation and fibrinolysis and-to establish the contribution of the mesothelium to the process. Complementary in vitro experiments will be used to define pathways of fibrin turnover by which mesothelial cells influence remodeling via the control of coagulation and regulation of proteolysis by urokinase and its receptor (uPAR). We will also determine the effect of uPAR on mesothelial cell functions including proliferation and migration and elucidate mechanisms which regulate uPAR expression. We will use a variety of protein chemistry, molecular biology and immunohistologic techniques to address these aims. Organization of the pleural compartment after injury leads to local scarring, with morbidity related to both restricted lung function and invasive therapeutic procedures. Our hypothesis is that pleural organization and scarring can be prevented selectively interfering with local fibrin formation and/or clearance. Our studies will define the role of these pathways in pleural organization and could provide novel clinical strategies to preempt or limit the process.