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Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation
by
Arecco, N.
, Jones, F. K.
, Beynon, R. J.
, Simpson, D. M.
, Mason, D.
, Clarke, C. J.
, Pisconti, A.
in
13/100
/ 13/106
/ 13/2
/ 13/51
/ 14/34
/ 14/63
/ 631/250/2504/223/1699
/ 631/532/2439
/ 64/60
/ 82/16
/ 82/29
/ 82/58
/ 96/2
/ 96/98
/ Animals
/ Cell Differentiation - drug effects
/ Cell Proliferation - drug effects
/ Cell Survival - drug effects
/ Cells, Cultured
/ Humanities and Social Sciences
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Mice, Inbred mdx
/ multidisciplinary
/ Muscle Fibers, Skeletal - cytology
/ Muscle Fibers, Skeletal - metabolism
/ Muscle, Skeletal - cytology
/ Muscle, Skeletal - metabolism
/ Muscular Dystrophy, Duchenne - metabolism
/ Muscular Dystrophy, Duchenne - pathology
/ Myoblasts - cytology
/ Myoblasts - drug effects
/ Myoblasts - metabolism
/ MyoD Protein - metabolism
/ Neutrophils - cytology
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Pancreatic Elastase - metabolism
/ Pancreatic Elastase - pharmacology
/ Phenotype
/ Proteome - analysis
/ Science
/ Science (multidisciplinary)
/ Serpins - metabolism
/ Substrate Specificity
/ Time Factors
2016
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Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation
by
Arecco, N.
, Jones, F. K.
, Beynon, R. J.
, Simpson, D. M.
, Mason, D.
, Clarke, C. J.
, Pisconti, A.
in
13/100
/ 13/106
/ 13/2
/ 13/51
/ 14/34
/ 14/63
/ 631/250/2504/223/1699
/ 631/532/2439
/ 64/60
/ 82/16
/ 82/29
/ 82/58
/ 96/2
/ 96/98
/ Animals
/ Cell Differentiation - drug effects
/ Cell Proliferation - drug effects
/ Cell Survival - drug effects
/ Cells, Cultured
/ Humanities and Social Sciences
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Mice, Inbred mdx
/ multidisciplinary
/ Muscle Fibers, Skeletal - cytology
/ Muscle Fibers, Skeletal - metabolism
/ Muscle, Skeletal - cytology
/ Muscle, Skeletal - metabolism
/ Muscular Dystrophy, Duchenne - metabolism
/ Muscular Dystrophy, Duchenne - pathology
/ Myoblasts - cytology
/ Myoblasts - drug effects
/ Myoblasts - metabolism
/ MyoD Protein - metabolism
/ Neutrophils - cytology
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Pancreatic Elastase - metabolism
/ Pancreatic Elastase - pharmacology
/ Phenotype
/ Proteome - analysis
/ Science
/ Science (multidisciplinary)
/ Serpins - metabolism
/ Substrate Specificity
/ Time Factors
2016
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Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation
by
Arecco, N.
, Jones, F. K.
, Beynon, R. J.
, Simpson, D. M.
, Mason, D.
, Clarke, C. J.
, Pisconti, A.
in
13/100
/ 13/106
/ 13/2
/ 13/51
/ 14/34
/ 14/63
/ 631/250/2504/223/1699
/ 631/532/2439
/ 64/60
/ 82/16
/ 82/29
/ 82/58
/ 96/2
/ 96/98
/ Animals
/ Cell Differentiation - drug effects
/ Cell Proliferation - drug effects
/ Cell Survival - drug effects
/ Cells, Cultured
/ Humanities and Social Sciences
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Mice, Inbred mdx
/ multidisciplinary
/ Muscle Fibers, Skeletal - cytology
/ Muscle Fibers, Skeletal - metabolism
/ Muscle, Skeletal - cytology
/ Muscle, Skeletal - metabolism
/ Muscular Dystrophy, Duchenne - metabolism
/ Muscular Dystrophy, Duchenne - pathology
/ Myoblasts - cytology
/ Myoblasts - drug effects
/ Myoblasts - metabolism
/ MyoD Protein - metabolism
/ Neutrophils - cytology
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Pancreatic Elastase - metabolism
/ Pancreatic Elastase - pharmacology
/ Phenotype
/ Proteome - analysis
/ Science
/ Science (multidisciplinary)
/ Serpins - metabolism
/ Substrate Specificity
/ Time Factors
2016
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Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation
Journal Article
Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation
2016
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Overview
In Duchenne muscular dystrophy, progressive loss of muscle tissue is accompanied by fibrosis, chronic inflammation and reduced muscle regenerative capacity. Although much is known about the development of fibrosis and chronic inflammation in muscular dystrophy, less is known about how they are mechanistically linked to loss of muscle regenerative capacity. We have developed a proteomics method to discover dystrophy-associated changes in the muscle progenitor cell niche, which identified serine proteases, and especially neutrophil elastase, as candidates. We show that elastase activity is increased in dystrophic (
mdx
4cv
) muscle and impairs myoblast survival in culture. While the effect of elastase on C2C12 cell survival correlates with the kinetics of elastase-mediated degradation of the substrate to which the cells adhere, the effect of elastase on satellite cell-derived primary myoblast growth and differentiation is substrate-independent and even more dramatic than the effect on C2C12 cells, suggesting a detrimental role for elastase on myogenesis
in vivo
. Additionally, elastase impairs differentiation of both primary and C2C12 myoblasts into myotubes. Our findings evidence the importance of neutrophil-mediated inflammation in muscular dystrophy and indicate elastase-mediated regulation of myoblast behaviour as a potential mechanism underlying loss of regenerative capacity in dystrophic muscle.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/2
/ 13/51
/ 14/34
/ 14/63
/ 64/60
/ 82/16
/ 82/29
/ 82/58
/ 96/2
/ 96/98
/ Animals
/ Cell Differentiation - drug effects
/ Cell Proliferation - drug effects
/ Cell Survival - drug effects
/ Humanities and Social Sciences
/ Male
/ Mice
/ Muscle Fibers, Skeletal - cytology
/ Muscle Fibers, Skeletal - metabolism
/ Muscle, Skeletal - metabolism
/ Muscular Dystrophy, Duchenne - metabolism
/ Muscular Dystrophy, Duchenne - pathology
/ Pancreatic Elastase - metabolism
/ Pancreatic Elastase - pharmacology
/ Science
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