title: Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Inflammation and Fibrosis of Skeletal Muscles.
abstract: In skeletal muscles, levels and activity of Matrix MetalloProteinases (MMPs) and Tissue Inhibitors of MetalloProteinases (TIMPs) have been involved in myoblast migration, fusion and various physiological and pathological remodeling situations including neuromuscular diseases. This has opened perspectives for the use of MMPs' overexpression to improve the efficiency of cell therapy in muscular dystrophies and resolve fibrosis. Alternatively, inhibition of individual MMPs in animal models of muscular dystrophies has provided evidence of beneficial, dual or adverse effects on muscle morphology or function. We review here the role played by MMPs/TIMPs in skeletal muscle inflammation and fibrosis, two major hurdles that limit the success of cell and gene therapy. We report and analyze the consequences of genetic or pharmacological modulation of MMP levels on the inflammation of skeletal muscles and their repair in light of experimental findings. We further discuss how the interplay between MMPs/TIMPs levels, cytokines/chemokines, growth factors and permanent low-grade inflammation favor cellular and molecular modifications resulting in fibrosis.
authors.affiliation: Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
authors.forename: Hala S
authors.initials: HS
authors.lastname: Alameddine
authors.affiliation: The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, UK.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Morgan
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D016207:Cytokines / Q000276:immunology; D005355:Fibrosis; D015316:Genetic Therapy; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D020782:Matrix Metalloproteinases / Q000276:immunology*; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology; D009136:Muscular Dystrophies / Q000276:immunology / Q000473:pathology / Q000628:therapy; D019714:Tissue Inhibitor of Metalloproteinases / Q000276:immunology*
chemical_list: D016207:Cytokines; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases
keywords: MMPs; TIMPs; diseases; fibrosis; inflammation; skeletal muscle