title: uPA deficiency exacerbates muscular dystrophy in MDX mice.
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.
authors.affiliation: Program on Differentiation and Cancer, Center for Genomic Regulation, E-08003, Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Suelves
authors.forename: Berta
authors.initials: B
authors.lastname: Vidal
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Serrano
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Josep
authors.initials: J
authors.lastname: Roma
authors.forename: Roser
authors.initials: R
authors.lastname: López-Alemany
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
authors.forename: María Martínez
authors.initials: MM
authors.lastname: de Lagrán
authors.forename: Angels
authors.initials: A
authors.lastname: Díaz-Ramos
authors.forename: Maria Angels
authors.initials: MA
authors.lastname: Díaz
authors.forename: Mercè
authors.initials: M
authors.lastname: Jardí
authors.forename: Manuel
authors.initials: M
authors.lastname: Roig
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Pura
authors.initials: P
authors.lastname: Muñoz-Cánoves
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032446:Myoblasts / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency*