Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration - CRCL-Sénescence, cancer et vieillissement Accéder directement au contenu
Article Dans Une Revue eLife Année : 2022

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

Michèle Mg Hillege
Andi Shi
Ricardo Galli
  • Fonction : Auteur
Gang Wu
  • Fonction : Auteur
Willem Mh Hoogaars
  • Fonction : Auteur
Richard Jaspers

Résumé

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.
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Dates et versions

hal-03766456 , version 1 (01-12-2023)

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Michèle Mg Hillege, Andi Shi, Ricardo Galli, Gang Wu, Philippe Bertolino, et al.. Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration. eLife, 2022, 11, ⟨10.7554/eLife.77610⟩. ⟨hal-03766456⟩
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