title: Pattern of metalloprotease activity and myofiber regeneration in skeletal muscles of mdx mice.
abstract: Matrix metalloproteases (MMPs) are key regulatory molecules in the formation, remodeling, and degradation of extracellular matrix components in both physiological and pathological processes. Skeletal muscles of mdx dystrophic mice show distinct patterns of inflammation and regeneration, suggesting that factors within the microenvironment influence the adaptive responses of muscles with predominantly slow-twitch or fast-twitch fibers. This study aimed to verify the pattern of MMP activity in gastrocnemius, soleus, and diaphragm muscles and correlate it with the regenerative capability at distinct stages of the mdx myopathy. Marked inflammation and myonecrosis was associated with increased MMP-9 activity and TNF-alpha (tumor necrosis factor-alpha) production, whereas muscle regeneration, evidenced by NCAM (neural cell adhesion molecule) expression and MMP-2 activity, varied at different stages of the disease. Soleus muscles showed a high percentage of NCAM-positive myofibers in the early stages (2 weeks) of the disease, but they appeared in the gastrocnemius muscles at 12 weeks and in the diaphragm at 24 weeks. Increased MMP-2 activity in the diaphragm throughout all stages of the disease suggests important tissue remodeling, which is probably associated with persistent inflammation. The results indicate that the microenvironment of distinct skeletal muscle may influence a particular kinetic pattern of MMP activity, which ultimately favors persistent inflammation and myofiber regeneration at different stages of the myopathy in mdx mice.
authors.affiliation: Department of Cellular and Molecular Biology, Institute of Biology Federal Fluminense University, Niterói, RJ 24210-150, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Bani
authors.forename: Jussara
authors.initials: J
authors.lastname: Lagrota-Candido
authors.forename: Douglas Florindo
authors.initials: DF
authors.lastname: Pinheiro
authors.forename: Paulo Emílio Correa
authors.initials: PE
authors.lastname: Leite
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Salimena
authors.forename: Andrea
authors.initials: A
authors.lastname: Henriques-Pons
authors.forename: Thereza
authors.initials: T
authors.lastname: Quirico-Santos
mesh_terms: D000367:Age Factors; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; D019002:CD56 Antigen; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9