Figure 7. Schematic diagram of the effects of single or combined muscle-specific knockout of Tgfbr1 and/or Acvr1b receptors on muscle hypertrophy, regeneration, and expression of ECM components.

(A) Myofibre size is not affected after individual knockout of Acvr1b or Tgfbr1, which indicates that these receptors have redundant effects on muscle size and that myostatin signals via both receptors to control muscle mass. Simultaneous knockout of both Acvr1b and Tgfbr1 inhibits signaling of TGF-β, myostatin and activin A and stimulates protein synthesis via the Akt/mTOR/p70S6K pathway, while inhibiting protein breakdown through repression of Trim63 levels, resulting in substantial muscle hypertrophy. (B) Upon acute injury, simultaneous knockout of combined Acvr1b and Tgfbr1 accelerates early muscle regeneration, as observed by increased myogenic gene expression as well as increased CSA of regenerating myofibres. An increased number of SCs likely contributes to these effects. (C) Simultaneous myofibre-specific knockout of Acvr1b and Tgfbr1 induces mRNA expression of ECM components. These effects are likely caused by enhanced TGF- β1 signaling in fibroblasts. Schematic is created using BioRender.