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Pattern of metalloprotease activity and myofiber regeneration in skeletal muscles of mdx mice
Author(s) -
Bani Cristiane,
LagrotaCandido Jussara,
Pinheiro Douglas Florindo,
Leite Paulo Emílio Correa,
Salimena Maria Cristina,
HenriquesPons Andrea,
QuiricoSantos Thereza
Publication year - 2008
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20970
Subject(s) - skeletal muscle , inflammation , regeneration (biology) , matrix metalloproteinase , myocyte , extracellular matrix , biology , myopathy , mdx mouse , neural cell adhesion molecule , microbiology and biotechnology , endocrinology , medicine , immunology , dystrophin , cell adhesion , cell , biochemistry
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‐α (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. Muscle Nerve, 2008