Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration

M. M.G. Hillege, A. Shi, R. A. Galli, G. Wu, P. Bertolino, W. M.H. Hoogaars, R. T. Jaspers*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Article numbere77610
Pages (from-to)1-32
Number of pages32
Publication statusPublished - 24 Mar 2022

Bibliographical note

Funding Information:
China Scholarship Council (CSC grant number 201808440351)

Publisher Copyright:
© 2022, eLife Sciences Publications Ltd. All rights reserved.


  • Cardiotoxin
  • Fibrosis
  • Hypertrophy
  • Inflammation
  • Injury
  • Myostatin
  • Skeletal muscle
  • TGF-β
  • Type I receptor


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