Myofibre-specific knockout of TGF-β type I receptors triggers muscle hypertrophy, promotes absolute force and oxidative metabolism

Transforming growth factor-β (TGF-β) signaling is associated with progressive skeletal muscle wasting. It is unknown whether myofibre-specific knockout of TGF-β type I receptors <i>Acvr1b</i> and <i>Tgfbr1</i> affects muscle transcriptome, mass, contractile force and oxidative metabolism. Here, we show that 3 months after myofibre-specific knockout of <i>Acvr1b</i> and <i>Tgfbr1</i> (dKO) in mice, gastrocnemius medialis demonstrated substantial differentially expressed genes, mainly related to muscle contraction, hypertrophy and oxidative metabolism. Muscle mass of gastrocnemius medialis in dKO mice was increased by 1.6-fold while maximal force was increased by 1.3-fold. Muscle mass of soleus in dKO mice was increased in proportion to maximal force (1.2-fold). The increase in myofibre cross-sectional area in dKO mice was accompanied by an increase in succinate dehydrogenase enzyme activity. Single receptor knockout caused minor phenotypical alterations. Our study highlights that myofibre-specific interference with both TGF-β type I receptors concurrently stimulates myofibre hypertrophy, promotes contractile force and mitochondrial activity.