| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Matrix metalloproteinases (MMPs) are enzymes having roles of extracellular matrix degradation and play an important role in tissue remodeling. We have reported that MMP-9 highly expressed in the skeletal muscle of dystrophin-deficient mice (mdx). In addition, MMP expression increased in experimental model for muscle necrosis and regeneration. We have therefore investigated whether MMPs participate in the pathogenesis in the dystrophin-deficient muscle from muscular dystrophy dog, CXMD_J. We found that mRNA levels of MMP-2, MMP-9 and MT1-MMP which conrols MMP-2 and -9, TIMP-1 and -2 which are endogenous inhibitors of MMP, significantly increased in the CXMD_J skeletal muscle. Gelatin zymography showed that activities of MMP-2 and -9 in the CXMD_J skeletal muscle were significantly higher than those from normal controls. In in-situ zymogram, MMP-2 and -9 localized at around the necrotic and regeneration fibers. MMP-9 immnocolocalized at infiltrated inflammation cells in the CXMD_J skeletal muscle, but it was difficult to evaluate immunolocalization of MMP-2 because of a problem in the antibody reactivity with CXMD_J. When we examined the MMP-2 localization using the experimental model for necrosis and regeneration in the normal mice or mdx mice, it located to mesenchymal fibroblastic cells around regeneration fibers. Furthermore, when MMP-2 expression was examined by RT-PCR on macrophage, muscle satellite cells or CD31(-)CD41(-) side population cells (SP cells) sorted by fluorescence activated cell sorting (FACS), MMP-2 expressed only in CD31(-)CD41(-)SP cells. Taken that CD31(-)CD45(-)SP cells have been reported to play a role in promotion of muscle regeneration, MMP-2 might participate in the remodeling of the extracellular matrix in skeletal muscle regeneration.
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