CONTROL OF FIBRIN TURNOVER IN PLEURAL DISEASE

临床和实验观察表明， 沉积在胸膜机化的发病机制中是重要的。 然而，对局部纤维蛋白周转的控制知之甚少 急性胸膜损伤和纤维化修复的过程中。我们将使用 建立家兔胸膜损伤模型，以确定体内机制 纤维蛋白的形成和纤维蛋白溶解， 对这个过程的影响。补充体外实验 将用于定义纤维蛋白周转的途径， 细胞通过控制凝血和调节来影响重塑 尿激酶及其受体（uPAR）的蛋白水解。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 表情我们将使用各种蛋白质化学、分子生物学 和免疫组织学技术来解决这些问题。组织 受伤后的胸膜室会导致局部疤痕， 与肺功能受限和侵入性肺损伤相关的发病率 治疗程序。我们的假设是胸膜组织和 选择性地干扰局部纤维蛋白， 形成和/或清除。 我们的研究将确定这些 胸膜组织的通路，并可以提供新的临床 战略抢占或限制的过程。

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.