uPA deficiency exacerbates muscular dystrophy in MDX mice-

Authors
M. Suelves, B. Vidal, A. L. Serrano, M. Tjwa, J. Roma et al.

Lab
Program on Differentiation and Cancer and Program on Genes and Disease, Center for Genomic Regulation, Barcelona, Spain ; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain

Journal
JCB

Abstract
Duchenne muscular dystrophy (DMD) 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 DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed 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.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)