uPA deficiency exacerbates muscular dystrophy in MDX mice
Open Access
- 4 September 2007
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 178 (6), 1039-1051
- https://doi.org/10.1083/jcb.200705127
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.Keywords
This publication has 76 references indexed in Scilit:
- Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesisThe Journal of Experimental Medicine, 2007
- TNF-α regulates myogenesis and muscle regeneration by activating p38 MAPKAmerican Journal of Physiology-Cell Physiology, 2007
- Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapyProceedings of the National Academy of Sciences of the United States of America, 2007
- Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivoThe Journal of Physiology, 2006
- Role of TNF-α signaling in regeneration of cardiotoxin-injured muscleAmerican Journal of Physiology-Cell Physiology, 2005
- The plasminogen activation system in skeletal muscle regeneration: antagonistic roles of urokinase-type plasminogen activator (upa) and its inhibitor (PAI-1)Frontiers in Bioscience-Landmark, 2005
- Urokinase is required for the formation of mactinin, an α-actinin fragment that promotes monocyte/macrophage maturationBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2002
- Plasmin activity is required for myogenesis in vitro and skeletal muscle regeneration in vivoBlood, 2002
- Urokinase-dependent plasminogen activation is required for efficient skeletal muscle regeneration in vivoBlood, 2001
- Involvement of the [uPAR:uPA:PAI-1:LRP] Complex in Human Myogenic Cell MotilityExperimental Cell Research, 2000