TY - JOUR
T1 - Osteopontin is highly expressed in severely dystrophic muscle and seems to play a role in muscle regeneration and fibrosis
AU - Zanotti, Simona
AU - Gibertini, Sara
AU - di Blasi, Claudia
AU - Cappelletti, Cristina
AU - Bernasconi, Pia
AU - Mantegazza, Renato
AU - Morandi, Lucia
AU - Mora, Marina
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Collagen
KW - Extracellular matrix
KW - Muscle fibrosis
KW - Muscular dystrophy osteopontin
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U2 - 10.1111/j.1365-2559.2011.04051.x
DO - 10.1111/j.1365-2559.2011.04051.x
M3 - Article
C2 - 22175901
AN - SCOPUS:84855946017
VL - 59
SP - 1215
EP - 1228
JO - Histopathology
JF - Histopathology
SN - 0309-0167
IS - 6
ER -