CONTROL OF FIBRIN TURNOVER IN PLEURAL DISEASE

University Of Texas Hlth Ctr At Tyler, Tyler TX

Investigators

Linked publications & trials

Abstract

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.