UPAR is not required for skeletal muscle regeneration

Abstract

Muscle regeneration has been shown to be severely impaired in urokinase-type plasminogen activator deficient (uPA-/-) mice, and the impaired regeneration was associated with a lack of macrophage accumulation following muscle injury. Many studies have demonstrated that the receptor for uPA (uPAR) plays an important role in inflammatory cell migration, by localizing the activity of uPA, as well as initiating signaling mechanisms, in migrating cells. The purpose of this study was to test the hypothesis that uPA/uPAR interactions are required for inflammatory cell accumulation following muscle injury and for muscle regeneration. Extensor digitorum longus (EDL) muscles were injured by cardiotoxin injection in uPAR-/- and wild-type (WT) mice. In WT mice, uPAR mRNA levels were elevated at 1 and 3d post-injury and then returned to baseline levels. Macrophage accumulation peaked 3 and 5 days post-injury in both uPAR-/- and WT mice, with no significant difference between groups. Histological analyses confirmed the efficient regeneration of both uPAR-/- and WT muscle with no difference seen in the number of regenerating fibers at 5d post-injury. These results demonstrate the interaction between uPA and uPAR is not required for the migration and accumulation of macrophages and subsequent regeneration in skeletal muscle following cardiotoxin-induced injury. Supported by NASA (GSRP) & Department of Defense (PRMRP).