Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration
- Vrije Universiteit Amsterdam, Netherlands
- Université de Lyon, UMR INSERM U1052, CNRS 5286, France
Abstract
In skeletal muscle, transforming growth factor-β (TGF-β) family growth factors, TGF-β1 and myostatin, are involved in atrophy and muscle wasting disorders. Simultaneous interference with their signalling pathways may improve muscle function, however little is known about their individual and combined receptor signalling. Here we show that inhibition of TGF-β signalling by simultaneous muscle-specific knockout of TGF-β type I receptors Tgfbr1 and Acvr1b in mice, induces substantial hypertrophy, while such effect does not occur by single receptor knockout. Hypertrophy is induced by increased phosphorylation of Akt and p70S6K and reduced E3 ligases expression, while myonuclear number remains unaltered. Combined knockout of both TGF-β type I receptors increases the number of satellite cells, macrophages and improves regeneration post cardiotoxin-induced injury by stimulating myogenic differentiation. Extra cellular matrix gene expression is exclusively elevated in muscle with combined receptor knockout. Tgfbr1 and Acvr1b are synergistically involved in regulation of myofibre size, regeneration and collagen deposition.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1 to 5.
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Data from: Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regenerationryad Digital Repository, doi:10.5061/dryad.jh9w0vtd5.
Article and author information
Author details
Michèle MG Hillege
Philippe Bertolino
Funding
Prinses Beatrix Spierfonds (W.OR14-17)
- Michèle MG Hillege
- Willem MH Hoogaars
- Richard T Jaspers
China Scholarship Council (201808440351))
- Andi Shi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were performed according to the national guidelines approved by the Central Committee for Animal Experiments (CCD) (AVD112002017862) and the Institute of Animal Welfare (IvD) of the Vrije Universiteit Amsterdam.
Copyright
© 2022, Hillege et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration
eLife 11:e77610.
https://doi.org/10.7554/eLife.77610
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