ArticleProceedings of the National Academy of Sciences of the United States of America2010
Hypoxia converts the myogenic action of insulin-like growth factors into mitogenic action by differentially regulating multiple signaling pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Hypoxic Signaling in Skeletal Muscle Maintenance and Regeneration: A Systematic Review.Frontiers in physiology · 2021Pooled it
- Skeletal Muscle miRNA Patterns in High-Altitude Trekkers: Exploratory Identification of Molecular Signatures of Cellular and Endocrine Adaptation.Biomolecules · 2026Article
- Transient hypoxia followed by progressive reoxygenation is required for muscle repair.EMBO reports · 2026Article
- Dairy byproducts as sustainable alternatives to FCS in 2D and 3D skeletal muscle cell cultures.Bioresources and bioprocessing · 2025Article
- Targeting therapy of PI3K/AKT signaling pathway via non-coding RNAs in diabetic retinopathy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Regulation of CMGC kinases by hypoxia.BMB reports · 2023Review
- Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting.International journal of molecular sciences · 2023Review
- Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation.PloS one · 2023Article
- Sphingosine-1-phosphate-lyase deficiency affects glucose metabolism in a way that abets oncogenesis.Molecular oncology · 2022Article
- The effect of hypoxia on myogenic differentiation and multipotency of the skeletal muscle-derived stem cells in mice.Stem cell research & therapy · 2022Article
- Oxygen supplementation to limit hypoxia-induced muscle atrophy in C2C12 myotubes: comparison with amino acid supplement and electrical stimulation.Cell and tissue research · 2022Article
- Article
- Biochemical indices, gene expression, and SNPs associated with salinity adaptation in juvenile chum salmon (PeerJ · 2022Article
- NADPH-Oxidase Derived Hydrogen Peroxide and Irs2b Facilitate Re-oxygenation-Induced Catch-Up Growth in Zebrafish Embryo.Frontiers in endocrinology · 2022Article
- Activation of ERK-Drp1 signaling promotes hypoxia-induced Aβ accumulation by upregulating mitochondrial fission and BACE1 activity.FEBS open bio · 2021Article
- Anemic hypoxemia reduces myoblast proliferation and muscle growth in late-gestation fetal sheep.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Age-related decline of interferon-gamma responses in macrophage impairs satellite cell proliferation and regeneration.Journal of cachexia, sarcopenia and muscle · 2020Article
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Bayesian Modeling Identifies PLAG1 as a Key Regulator of Proliferation and Survival in Rhabdomyosarcoma Cells.Molecular cancer research : MCR · 2020Article
- Increase in HDAC9 suppresses myoblast differentiation via epigenetic regulation of autophagy in hypoxia.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin-like growth factors (IGFs) stimulate myoblast proliferation and differentiation. It remains elusive how these mutually exclusive cellular responses are elicited by the same growth factor. Here we report that whereas IGF promotes myoblast differentiation under normoxia, it stimulates proliferation under hypoxia. Hypoxia activates the HIF-1 transcriptional program and knockdown of HIF-1alpha changes the mitogenic action of IGF into myogenic action under hypoxia. Conversely, overexpression of HIF-1alpha abolishes the myogenic effect of IGF under normoxia. Under normoxia, IGF activates the Akt-mTOR, p38, and Erk1/2 MAPK pathways. Hypoxia suppresses basal and IGF-induced Akt-mTOR and p38 activity, whereas it enhances and prolongs IGF-induced Erk1/2 activation in a HIF-1-dependent fashion. Activation of Akt-mTOR and p38 promotes myogenesis, and p38 also inhibits proliferation. Activation of Erk stimulates myoblast proliferation but inhibits differentiation. These results suggest that hypoxia converts the myogenic action of IGFs into mitogenic action by differentially regulating multiple signaling pathways via HIF-1-dependent mechanisms. Our findings provide a mechanistic explanation for the paradoxical actions of IGFs during myogenesis and reveal a novel mechanism by which cells sense and integrate growth factor signals and oxygen availability in their microenvironments.
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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.