Turner et al., (2021). Mechanical loading of bioengineered skeletal muscle in vitro recapitulates gene expression signatures of resistance exercise in vivo.pdf (4.35 MB)

Mechanical loading of bioengineered skeletal muscle in vitro recapitulates gene expression signatures of resistance exercise in vivo

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posted on 23.02.2021, 16:20 by Daniel C Turner, Piotr P Gorski, Robert A Seaborne, Mark Viggars, Mark Murphy, Jonathan C Jarvis, Neil Martin, Claire E Stewart, Adam P Sharples
Understanding the role of mechanical loading and exercise in skeletal muscle (SkM) is paramount for delineating the molecular mechanisms that govern changes in muscle mass. However, it is unknown whether loading of bioengineered SkM in vitro adequately recapitulates the molecular responses observed after resistance exercise (RE) in vivo. To address this, the transcriptional and epigenetic (DNA methylation) responses were compared after mechanical loading in bioengineered SkM in vitro and after RE in vivo. Specifically, genes known to be upregulated/hypomethylated after RE in humans were analyzed. Ninety‐three percent of these genes demonstrated similar changes in gene expression post‐loading in the bioengineered muscle when compared to acute RE in humans. Furthermore, similar differences in gene expression were observed between loaded bioengineered SkM and after programmed RT in rat SkM tissue. Hypomethylation occurred for only one of the genes analysed (GRIK2) post‐loading in bioengineered SkM. To further validate these findings, DNA methylation and mRNA expression of known hypomethylated and upregulated genes post‐acute RE in humans were also analyzed at 0.5, 3, and 24 h post‐loading in bioengineered muscle. The largest changes in gene expression occurred at 3 h, whereby 82% and 91% of genes responded similarly when compared to human and rodent SkM respectively. DNA methylation of only a small proportion of genes analyzed (TRAF1, MSN, and CTTN) significantly increased post‐loading in bioengineered SkM alone. Overall, mechanical loading of bioengineered SkM in vitro recapitulates the gene expression profile of human and rodent SkM after RE in vivo. Although some genes demonstrated differential DNA methylation post‐loading in bioengineered SkM, such changes across the majority of genes analyzed did not closely mimic the epigenetic response to acute‐RE in humans.

Funding

Liverpool John Moores University

Society for Endocrinology

Norges Idrettshøgskole

Engineering and Physical Sciences Research Council

Keele University

North Staffordshire Medical Institute

GlaxoSmithKline

History

School

  • Sport, Exercise and Health Sciences

Published in

Journal of Cellular Physiology

Publisher

Wiley

Version

VoR (Version of Record)

Rights holder

© The Authors

Publisher statement

This is an Open Access Article. It is published by Wiley under the Creative Commons Attribution 4.0 International Licence (CC BY 4.0). Full details of this licence are available at: https://creativecommons.org/licenses/by/4.0/

Acceptance date

03/02/2021

Publication date

2021-02-15

Copyright date

2021

ISSN

0021-9541

eISSN

1097-4652

Language

en

Depositor

Dr Neil Martin. Deposit date: 23 February 2021

Licence

Exports