Mtor is necessary for proper satellite cell activity and skeletal muscle regeneration
Open accessAbstract
The serine/threonine kinase mammalian target of rapamycin (mTOR) is a key regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive deletion of Mtor gene results in embryonic lethality, the function of mTOR in muscle stem cells (satellite cells) and skeletal muscle regeneration remains to be determined. In this study, we established a satellite cell specific Mtor conditional knockout (cKO) mouse model by crossing Pax7(CreER) and Mtor(flox/flox) mice. Skeletal muscle regeneration after injury was severely compromised in the absence of Mtor, indicated by increased number of necrotic myofibers infiltrated by Evans blue dye, and reduced number and size of regenerated myofibers in the Mtor cKO mice compared to wild type (WT) littermates. To dissect the cellular mechanism, we analyzed satellite cell-derived primary myoblasts grown on single myofibers or adhered to culture plates. The Mtor cKO myoblasts exhibited defective proliferation and differentiation kinetics when compared to myoblasts derived from WT littermates. At the mRNA and protein levels, the Mtor cKO myoblasts expressed lower levels of key myogenic determinant genes Pax7, Myf5, Myod, Myog than did the WT myoblasts. These results suggest that mTOR is essential for satellite cell function and skeletal muscle regeneration through controlling the expression of myogenic genes.
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Activation of mTOR and its downstream targets p70S6K1 and 4E-BP1 is involved in regulation of translation initiation responses required for skeletal muscle growth, hypertrophy, and myogenesis.
“Activation of the mechanistic target of rapamycin (mTOR) and its downstream signalling targets the 70 kDa ribosomal protein S6 kinase-1 (p70S6K1) and eIF4E-binding protein 1 (4E-BP1) are involved in the regulation of translation initiation responses that are required for skeletal muscle growth, hypertrophy, and also have a role in myogenesis [121].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [121]
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- Authors
- Zhang, P., Liang, X., Shan, T., Jiang, Q., Deng, C., Zheng, R., & Kuang, S.
- Affiliations
- Huazhong Agricultural University (CN)
- Purdue University West Lafayette (US)
- Guangxi University (CN)
- Corresponding author
- Zheng, Rong
- Kuang, Shihuan
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 463
- Issue
- 1-2
- Pages
- 102-108
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC4484853
- OpenAlex
- W281681086
- Cited by
- 133
- References
- 29
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 11 · 2023: 13 · 2022: 18 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 10 · 2017: 11 · 2016: 7 · 2015: 1
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health of USA (AR060652)
- National Key Technology Support Program of China (2014BAD20B01)
- Science and Technology Department of Hubei Province, China (2013BBA057)
- China Scholarship Council (201206760022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTOR, satellite cells, skeletal muscle regeneration, muscle stem cells, conditional knockout mice, Pax7, myoblast proliferation, myogenesis, myogenic gene expression, muscle damage, protein synthesis
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Regeneration, RNA, Messenger, Wound Healing, MyoD Protein, Myogenin, Mice, Knockout, Muscle, Skeletal, Muscle Development, Satellite Cells, Skeletal Muscle, Cell Proliferation, Mice, PAX7 Transcription Factor, Myogenic Regulatory Factor 5, TOR Serine-Threonine Kinases
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