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Title: Hypoxia impairs muscle function and reduces myotube size in tissue engineered skeletal muscle
Authors: Martin, Neil R.W.
Aguilar-Agon, K.
Robinson, G.P.
Player, Darren J.
Turner, Mark C.
Myers, S.D.
Lewis, Mark P.
Issue Date: 2017
Publisher: Wiley (© the authors)
Citation: MARTIN, N.R.W. ... et al, 2017. Hypoxia impairs muscle function and reduces myotube size in tissue engineered skeletal muscle. Journal of Cellular Biochemistry, DOI: 10.1002/jcb.25982
Abstract: Contemporary tissue engineered skeletal muscle models display a high degree of physiological accuracy compared with native tissue, and therefore may be excellent platforms to understand how various pathologies affect skeletal muscle. Chronic obstructive pulmonary disease (COPD) is a lung disease which causes tissue hypoxia and is characterised by muscle fibre atrophy and impaired muscle function. In the present study we exposed engineered skeletal muscle to varying levels of oxygen (O2; 21-1%) for 24 hours in order to see if a COPD like muscle phenotype could be recreated in vitro, and if so, at what degree of hypoxia this occured. Maximal contractile force was attenuated in hypoxia compared to 21% O2; with culture at 5 and 1% O2 causing the most pronounced effects with 62 and 56% decrements in force respectively. Furthermore at these levels of O2, myotubes within the engineered muscles displayed significant atrophy which was not seen at higher O2 levels. At the molecular level we observed increases in mRNA expression of MuRF-1 only at 1% O2 whereas MAFbx expression was elevated at 10, 5 and 1% O2. In addition, p70S6 kinase phosphorylation (a downstream effector of mTORC1) was reduced when engineered muscle was cultured at 1%, with no significant changes seen above this O2 level. Overall, these data suggest that engineered muscle exposed to O2 levels of ≤5% adapts in a manner similar to that seen in COPD patients, and thus may provide a novel model for further understanding muscle wasting associated with tissue hypoxia.
Description: This is an Open Access article published by Wiley and distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0). More details are available here: https://creativecommons.org/licenses/by/4.0/
Sponsor: This article was funded by the RCUK under grant number EP/L015072/1.
Version: Accepted for publication
DOI: 10.1002/jcb.25982
URI: https://dspace.lboro.ac.uk/2134/24585
Publisher Link: http://dx.doi.org/10.1002/jcb.25982
ISSN: 1097-4644
Appears in Collections:Published Articles (Sport, Exercise and Health Sciences)

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