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<p>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 affects muscle transcriptome, mass, contractile force and oxidative metabolism. Here we show that 3 months after myofibre-specific knockout of TGF-β type I receptors (dKO) in male mice, transcriptomics demonstrate substantially more differentially expressed genes in gastrocnemius medialis (GM) than in soleus, mainly related to muscle contraction, hypertrophy and oxidative metabolism. GM&#xa0;mass of dKO mice increases substantially more than maximal force. Conversely, soleus mass of dKO mice&#xa0;increases in proportion to maximal force. Myofibre hypertrophy in dKO mice is accompanied by a proportional increase in succinate dehydrogenase enzyme activity. These adaptations are associated with a simultaneous decrease in β1-syntrophin and increases in sarcolipin, hepatocyte growth factor gene expression and anabolic signalling. Single receptor knockout causes minor phenotypical and transcriptional alterations. Our study highlights that myofibre-specific interference with both TGF-β type I receptors concurrently stimulates myofibre hypertrophy, enhances absolute force and simultaneously augments oxidative capacity.</p><p></p>

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Myofiber-specific knockout of TGF-β type I receptors in mice concurrently drives muscle hypertrophy, oxidative metabolism, and absolute force

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月3日

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  • Andi Shi,
  • Michèle M. G. Hillege,
  • Wendy Noort,
  • Carla Offringa,
  • Gang Wu,
  • Tim Forouzanfar,
  • Willem M. H. Hoogaars,
  • Rob C. I. Wüst,
  • Richard T. Jaspers

摘要

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 affects muscle transcriptome, mass, contractile force and oxidative metabolism. Here we show that 3 months after myofibre-specific knockout of TGF-β type I receptors (dKO) in male mice, transcriptomics demonstrate substantially more differentially expressed genes in gastrocnemius medialis (GM) than in soleus, mainly related to muscle contraction, hypertrophy and oxidative metabolism. GM mass of dKO mice increases substantially more than maximal force. Conversely, soleus mass of dKO mice increases in proportion to maximal force. Myofibre hypertrophy in dKO mice is accompanied by a proportional increase in succinate dehydrogenase enzyme activity. These adaptations are associated with a simultaneous decrease in β1-syntrophin and increases in sarcolipin, hepatocyte growth factor gene expression and anabolic signalling. Single receptor knockout causes minor phenotypical and transcriptional alterations. Our study highlights that myofibre-specific interference with both TGF-β type I receptors concurrently stimulates myofibre hypertrophy, enhances absolute force and simultaneously augments oxidative capacity.