ArticleAmerican journal of physiology. Cell physiology2009
mTOR regulates skeletal muscle regeneration in vivo through kinase-dependent and kinase-independent mechanisms.
Article in American journal of physiology. Cell physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 149 citations in OpenAlex.
- Mechanisms of Impaired Skeletal Muscle Regeneration and Therapeutic Approaches in Aging and Chronic Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Persistent Human Quadriceps Muscle Volume Deficits Following ACL Reconstruction Are Associated With No Detectable Between-Leg Differences in Vastus Lateralis Muscle Signaling at Rest or Immediately Following Resistance Exercise.Scandinavian journal of medicine & science in sports · 2026Article
- Loss of LanC-like proteins delays post-injury regeneration of aging skeletal muscles.bioRxiv : the preprint server for biology · 2026Article
- HuR-mediated regulation of mTOR mRNA stability promotes the commitment of satellite cells towards myogenesis.Cell death & disease · 2026Article
- Ageing-Associated Dysregulation of Myogenic Differentiation in Inclusion Body Myositis.Journal of cachexia, sarcopenia and muscle · 2026Review
- The Integrated Stress Response Pathway Improves Aged Murine Muscle Stem Cell Activation andbioRxiv : the preprint server for biology · 2025Article
- mRNA translational control of regeneration.Current opinion in genetics & development · 2025Review
- β-hydroxy-β-methylbutyrate supplementation mitigates muscle atrophy induced by inactivity and protein deprivation.Biogerontology · 2025Article
- Muscle mTOR controls iron homeostasis and ferritinophagy via NRF2, HIFs and AKT/PKB signaling pathways.Cellular and molecular life sciences : CMLS · 2025Article
- Nutritional Interventions to Attenuate Quadriceps Muscle Deficits following Anterior Cruciate Ligament Injury and Reconstruction.Sports medicine (Auckland, N.Z.) · 2025Review
- Article
- Conditioned serum-free culture medium accomplishes adhesion and proliferation of bovine myogenic cells on uncoated dishes.NPJ science of food · 2024Article
- Effect of spermidine intake on skeletal muscle regeneration after chemical injury in male mice.Physiological reports · 2024Article
- Sex, tissue, and mitochondrial interactions modify the transcriptional response to rapamycin in Drosophila.BMC genomics · 2024Article
- Skeletal muscle regeneration after extensive cryoinjury of caudal myomeres in adult zebrafish.NPJ Regenerative medicine · 2024Article
- Unbiased evaluation of rapamycin's specificity as an mTOR inhibitor.Aging cell · 2023Article
- Muscle regeneration in gilthead sea bream: Implications of endocrine and local regulatory factors and the crosstalk with bone.Frontiers in endocrinology · 2023Article
- The Importance of mTORC1-Autophagy Axis for Skeletal Muscle Diseases.International journal of molecular sciences · 2022Review
- Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy andActa biochimica et biophysica Sinica · 2022Article
- Local problems need global solutions: The metabolic needs of regenerating organisms.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2022Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Rapamycin-sensitive signaling is required for skeletal muscle differentiation and remodeling. In cultured myoblasts, the mammalian target of rapamycin (mTOR) has been reported to regulate differentiation at different stages through distinct mechanisms, including one that is independent of mTOR kinase activity. However, the kinase-independent function of mTOR remains controversial, and no in vivo studies have examined those mTOR myogenic mechanisms previously identified in vitro. In this study, we find that rapamycin impairs injury-induced muscle regeneration. To validate the role of mTOR with genetic evidence and to probe the mechanism of mTOR function, we have generated and characterized transgenic mice expressing two mutants of mTOR under the control of human skeletal actin (HSA) promoter: rapamycin-resistant (RR) and RR/kinase-inactive (RR/KI). Our results show that muscle regeneration in rapamycin-administered mice is restored by RR-mTOR expression. In the RR/KI-mTOR mice, nascent myofiber formation during the early phase of regeneration proceeds in the presence of rapamycin, but growth of the regenerating myofibers is blocked by rapamycin. Igf2 mRNA levels increase drastically during early regeneration, which is sensitive to rapamycin in wild-type muscles but partially resistant to rapamycin in both RR- and RR/KI-mTOR muscles, consistent with mTOR regulation of Igf2 expression in a kinase-independent manner. Furthermore, systemic ablation of S6K1, a target of mTOR kinase, results in impaired muscle growth but normal nascent myofiber formation during regeneration. Therefore, mTOR regulates muscle regeneration through kinase-independent and kinase-dependent mechanisms at the stages of nascent myofiber formation and myofiber growth, respectively.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.