Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation

Arecco, N, Clarke, CJ, Jones, FK, Simpson, DM ORCID: 0000-0002-3962-4895, Mason, D ORCID: 0000-0002-8773-5274, Beynon, RJ ORCID: 0000-0003-0857-495X and Pisconti, A (2016) Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation. SCIENTIFIC REPORTS, 6 (1). 24708-.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Muscle, Skeletal, Neutrophils, Cells, Cultured, Myoblasts, Animals, Mice, Inbred C57BL, Mice, Inbred mdx, Mice, Muscular Dystrophy, Duchenne, Pancreatic Elastase, MyoD Protein, Proteome, Serpins, Cell Differentiation, Cell Proliferation, Cell Survival, Substrate Specificity, Phenotype, Time Factors, Male, Muscle Fibers, Skeletal
Depositing User:	Symplectic Admin
Date Deposited:	25 Jan 2019 09:50
Last Modified:	19 Jan 2023 01:08
DOI:	10.1038/srep24708
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3030751

Available Versions of this Item

• Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation. (deposited 17 May 2016 14:16)
  • Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation. (deposited 25 Jan 2019 09:50) [Currently Displayed]