Enhancement of Skeletal Muscle Repair by the Urokinase Type Plasminogen Activator System; Annual rept. 1 Jan-31 Dec 2006

摘要

Skeletal muscle injuries, caused by intense exercise or trauma, are among the most common injuries in military personnel. Enhancement of muscle repair following injury would minimize time lost and maximize performance during training and combat. We and others have published data demonstrating that the extracellular protease urokinase-type plasminogen activator (uPA) is required for efficient muscle repair, although the underlying mechanisms remain to be elucidated. In the present project, immunofluorescence analysis demonstrated that cell proliferation and satellite cell accumulation is impaired in uPA null mice, and accelerated in mice deficient in the inhibitor of uPA, PAI-1, compared to wild-type mice. Western blot analysis indicated that levels of active hepatocyte growth factors (HGF) are enhanced in PAI-1 null mice compared with wild-type mice, and that phosphorylation of the receptor of HGF, c-met, is similarly enhanced. Taken together, these data indicate that satellite cell activity is regulated by the balance of uPA and PAI-1, perhaps through activation of HGF. Findings from continued work on this project will provide insight into potential manipulation of components of the plasminogen system as a way to enhance muscle repair. Enhancing muscle repair following injury would minimize time lost due to muscle injury both during training and combat, and maximize performance following return from injury.