| Title: |
Genetic reduction of the extracellular matrix protein versican attenuates inflammatory cell infiltration and improves contractile function in dystrophic mdx diaphragm muscles. |
| Authors: |
McRae, Natasha L.1, Addinsall, Alex B.1,2 alex.addinsall@ki.se, Howlett, Kirsten F.3, McNeill, Bryony1, McCulloch, Daniel R.1, Stupka, Nicole1,4,5 nicole.stupka@unimelb.edu.au |
| Source: |
Scientific Reports. 7/6/2020, Vol. 10 Issue 1, p1-19. 19p. |
| Subject Terms: |
*EXTRACELLULAR matrix proteins, *VERSICAN, *DUCHENNE muscular dystrophy, *MUSCLE contraction, *PHYSICAL activity, *INFLAMMATION |
| Abstract: |
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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Scientific Reports is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
