Myofiber-specific knockout of TGF-β type I receptors in mice concurrently drives muscle hypertrophy, oxidative metabolism, and absolute force
Year: 2025
Type: article
Abstract: 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 Acvr1b and Tgfbr1 affects muscle transcriptome, mass, contractile force and oxidative metabolism. Here, we show that 3 months after myofibre-specific knockout of Acvr1b and Tgfbr1 (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.
Source: Figshare
Author: Shi, Andi
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7084063315
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