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Genetic reduction of the extracellular matrix protein versican attenuates inflammatory cell infiltration and improves contractile function in dystrophic mdx diaphragm muscles

McRae, Natasha L., Addinsall, Alex B., Howlett, Kirsten F., McNeill, Bryony, McCulloch, Daniel R. and Stupka, Nicole 2020, Genetic reduction of the extracellular matrix protein versican attenuates inflammatory cell infiltration and improves contractile function in dystrophic mdx diaphragm muscles, Scientific Reports, vol. 10, no. 1, pp. 1-19, doi: 10.1038/s41598-020-67464-x.

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Title Genetic reduction of the extracellular matrix protein versican attenuates inflammatory cell infiltration and improves contractile function in dystrophic mdx diaphragm muscles
Author(s) McRae, Natasha L.
Addinsall, Alex B.
Howlett, Kirsten F.ORCID iD for Howlett, Kirsten F. orcid.org/0000-0002-8571-4867
McNeill, BryonyORCID iD for McNeill, Bryony orcid.org/0000-0002-1580-2925
McCulloch, Daniel R.
Stupka, NicoleORCID iD for Stupka, Nicole orcid.org/0000-0002-1000-1707
Journal name Scientific Reports
Volume number 10
Issue number 1
Article ID 11080
Start page 1
End page 19
Total pages 19
Publisher Nature Research
Place of publication Berlin, Germany
Publication date 2020-07-06
ISSN 2045-2322
Keyword(s) Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
DUCHENNE MUSCULAR-DYSTROPHY
RESTING ENERGY-EXPENDITURE
SKELETAL-MUSCLE
CHONDROITIN SULFATE
TRANSFORMING GROWTH-FACTOR-BETA-1
MITOCHONDRIAL DYSFUNCTION
DIFFERENTIAL REGULATION
MOUSE MODEL
EXPRESSION
MICE
Summary There is a persistent, aberrant accumulation of V0/V1 versican in skeletal muscles from patients with Duchenne muscular dystrophy and in diaphragm muscles from mdx mice. Versican is a provisional matrix protein implicated in fibrosis and inflammation in various disease states, yet its role in the pathogenesis of muscular dystrophy is not known. Here, female mdx and male hdf mice (haploinsufficient for the versican allele) were bred. In the resulting F1 mdx-hdf male pups, V0/V1 versican expression in diaphragm muscles was decreased by 50% compared to mdx littermates at 20–26 weeks of age. In mdx-hdf mice, spontaneous physical activity increased by 17% and there was a concomitant decrease in total energy expenditure and whole-body glucose oxidation. Versican reduction improved the ex vivo strength and endurance of diaphragm muscle strips. These changes in diaphragm contractile properties in mdx-hdf mice were associated with decreased monocyte and macrophage infiltration and a reduction in the proportion of fibres expressing the slow type I myosin heavy chain isoform. Given the high metabolic cost of inflammation in dystrophy, an attenuated inflammatory response may contribute to the effects of versican reduction on whole-body metabolism. Altogether, versican reduction ameliorates the dystrophic pathology of mdx-hdf mice as evidenced by improved diaphragm contractile function and increased physical activity.
Language eng
DOI 10.1038/s41598-020-67464-x
Indigenous content off
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, The Author(s)
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30139794

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.