Myofiber-specific knockout of TGF-β type I receptors in mice concurrently drives muscle hypertrophy, oxidative metabolism, and absolute force
5 affiliations
- 1Department of Prosthodontics, School and Hospital of Stomatology, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Medical University, Guangzhou, China
- 2Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
- 3Savid School of Stomatology, Hangzhou Medical College, Hangzhou, China
- 4Department of Oral and Maxillofacial Surgery, Leiden University Medical Center (LUMC), Leiden, The Netherlands
- 5Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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 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.
Related
- Single-Nucleus RNA Sequencing Identifies CREM as a Brake on Myofiber Hypertrophy in Chickens.
- Thromboxane A2 receptor signalling amplifies osteoclastogenesis in rheumatoid arthritis through ACSL1 associated mitochondrial oxidative metabolism
- Histopathology and spatial transcriptomics jointly map myofiber-specific pathological programs in mTORC1-driven myopathy
- Ginseng derived extracellular vesicles attenuate adipocyte hypertrophy and modulate gut microbiota and cholecystokinin responsiveness in high fat diet fed mice
- Distinct muscle stem cell fates correlated with hyperplasia and hypertrophy during skeletal muscle growth in rainbow trout
BibTeX
@article{shi2026myofiberspecific,
title = {{Myofiber-specific knockout of TGF-β type I receptors in mice concurrently drives muscle hypertrophy, oxidative metabolism, and absolute force}},
author = {Andi Shi and Michèle M. G. Hillege and Wendy Noort and Carla Offringa and Gang Wu and Tim Forouzanfar and Willem M. H. Hoogaars and Rob C. I. Wüst and Richard T. Jaspers},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10501-8},
url = {https://doi.org/10.1038/s42003-026-10501-8},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Myofiber-specific knockout of TGF-β type I receptors in mice concurrently drives muscle hypertrophy, oxidative metabolism, and absolute force
AU - Andi Shi
AU - Michèle M. G. Hillege
AU - Wendy Noort
AU - Carla Offringa
AU - Gang Wu
AU - Tim Forouzanfar
AU - Willem M. H. Hoogaars
AU - Rob C. I. Wüst
AU - Richard T. Jaspers
PY - 2026
DA - 2026/07/03
JO - Communications Biology
DO - 10.1038/s42003-026-10501-8
UR - https://doi.org/10.1038/s42003-026-10501-8
AB - 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.
SN - 2399-3642
ER -