AIMS: To increase our understanding of profibrotic mechanisms in dystrophic muscle. METHODS AND RESULTS: Extracellular matrix, fibrosis-related molecules and histopathology were assessed in skeletal muscle of patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy type 1A (MDC1A).Osteopontin expression was much higher in DMD and MDC1A than in BMD and control muscle. Osteopontin was expressed in mononuclear cell infiltrates, on some muscle fibre surfaces, in regenerating fibres, and in calcified fibres. In all pathological muscles, matrix metalloproteinase (MMP)-1 was increased around groups of fibres that were also characterized by absence of collagen 1. The amounts of MMP-2, MMP-9 and tissue inhibitor of MMP -1 transcripts were also increased, whereas their proteins were variably expressed in muscle fibres (surface or cytoplasm) and at foci of necrosis and regeneration. Inflammatory cells, fibroblasts and myofibroblasts were more numerous in DMD and MDC1A than in BMD muscle. CONCLUSIONS: Several fibrosis-related factors are greatly altered in severely dystrophic skeletal muscle. Osteopontin was the most conspicuously upregulated, both as transcript and as protein, in muscle fibres and infiltrating cells, indicating an intimate involvement in fibrosis, and also in inflammation and muscle regeneration, although its precise roles in these processes remain to be elucidated.
AIMS: To increase our understanding of profibrotic mechanisms in dystrophic muscle. METHODS AND RESULTS: Extracellular matrix, fibrosis-related molecules and histopathology were assessed in skeletal muscle of patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy type 1A (MDC1A).Osteopontin expression was much higher in DMD and MDC1A than in BMD and control muscle. Osteopontin was expressed in mononuclear cell infiltrates, on some muscle fibre surfaces, in regenerating fibres, and in calcified fibres. In all pathological muscles, matrix metalloproteinase (MMP)-1 was increased around groups of fibres that were also characterized by absence of collagen 1. The amounts of MMP-2, MMP-9 and tissue inhibitor of MMP -1 transcripts were also increased, whereas their proteins were variably expressed in muscle fibres (surface or cytoplasm) and at foci of necrosis and regeneration. Inflammatory cells, fibroblasts and myofibroblasts were more numerous in DMD and MDC1A than in BMD muscle. CONCLUSIONS: Several fibrosis-related factors are greatly altered in severely dystrophic skeletal muscle. Osteopontin was the most conspicuously upregulated, both as transcript and as protein, in muscle fibres and infiltrating cells, indicating an intimate involvement in fibrosis, and also in inflammation and muscle regeneration, although its precise roles in these processes remain to be elucidated.
Authors: Tony Huynh; Kitipong Uaesoontrachoon; James L Quinn; Kathleen S Tatem; Christopher R Heier; Jack H Van Der Meulen; Qing Yu; Mark Harris; Christopher J Nolan; Guy Haegeman; Miranda D Grounds; Kanneboyina Nagaraju Journal: J Pathol Date: 2013-10 Impact factor: 7.996
Authors: Amy S Rosenberg; Montserrat Puig; Kanneboyina Nagaraju; Eric P Hoffman; S Armando Villalta; V Ashutosh Rao; Lalage M Wakefield; Janet Woodcock Journal: Sci Transl Med Date: 2015-08-05 Impact factor: 17.956
Authors: Michael G Poulos; Ranjan Batra; Moyi Li; Yuan Yuan; Chaolin Zhang; Robert B Darnell; Maurice S Swanson Journal: Hum Mol Genet Date: 2013-05-08 Impact factor: 6.150
Authors: Maria Laura Jorge Micheletto; Tulio de Almeida Hermes; Bruno Machado Bertassoli; Giuliana Petri; Matheus Moreira Perez; Fernando Luiz Affonso Fonseca; Alzira Alves de Siqueira Carvalho; David Feder Journal: Int J Exp Pathol Date: 2020-12-09 Impact factor: 1.925