Journal of Cell Biology vol:178 issue:6 pages:1039-1051
Duchenne muscular dystrophy (l is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of l The expression of uPA is induced in mdx cl strophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular [unction. Bone marrow (BM) transplantation experiments ravealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy.