ArticleThe Journal of biological chemistry2015
Hypoxia Inhibits Myogenic Differentiation through p53 Protein-dependent Induction of Bhlhe40 Protein.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- Hypoxic Signaling in Skeletal Muscle Maintenance and Regeneration: A Systematic Review.Frontiers in physiology · 2021Pooled it
- A systematic review of p53 regulation of oxidative stress in skeletal muscle.Redox report : communications in free radical research · 2018Pooled it
- Slow and fast locomotor muscle adaptations to sustained intermittent hypoxaemia.The journal of physiological sciences : JPS · 2026Article
- Phase-specific polarization of peripheral helper T cells influences immunopathology and viral control in HBV infection.Hepatology international · 2026Article
- Hypoxia-responsive interaction between P-TEFb, BHLHE40, and Tim8-Tim13 regulates hypoxic gene transcription.Science advances · 2026Article
- Transient hypoxia followed by progressive reoxygenation is required for muscle repair.EMBO reports · 2026Article
- An epigenetic perspective on neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy.Clinical epigenetics · 2025Review
- Adaptation responses to salt stress in the gut ofAnimal cells and systems · 2025Article
- Identification of Hypoxia-ALCAMAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs.Cancer research · 2024Article
- Chronic hypoxia impairs skeletal muscle repair via HIF-2α stabilization.Journal of cachexia, sarcopenia and muscle · 2024Article
- The role of oxygen tension in cell fate and regenerative medicine: implications of hypoxia/hyperoxia and free radicals.Cell and tissue banking · 2024Review
- FunctionalScience advances · 2024Article
- [Progress of pathogenesis and genetics of alcohol-induced osteonecrosis of femoral head].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2022Review
- Muscle dysfunction in the long coronavirus disease 2019 syndrome: Pathogenesis and clinical approach.Reviews in medical virology · 2022Review
- Hypoxia is fine-tuned by Hif-1α and regulates mesendoderm differentiation through the Wnt/β-Catenin pathway.BMC biology · 2022Article
- Muscle Wasting in Chronic Obstructive Pulmonary Disease: Not Enough Autophagy?American journal of respiratory cell and molecular biology · 2022Article
- MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40.Yonsei medical journal · 2022Article
- Comparative transcriptomic analysis of the brain in Takifugu rubripes shows its tolerance to acute hypoxia.Fish physiology and biochemistry · 2021Article
- Hypoxia and Hypoxia-Inducible Factor Signaling in Muscular Dystrophies: Cause and Consequences.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Satellite cells are muscle-resident stem cells capable of self-renewal and differentiation to repair injured muscles. However, muscle injury often leads to an ischemic hypoxia environment that impedes satellite cell differentiation and reduces the efficiency of muscle regeneration. Here we performed microarray analyses and identified the basic helix-loop-helix family transcription factor Bhlhe40 as a candidate mediator of the myogenic inhibitory effect of hypoxia. Bhlhe40 is strongly induced by hypoxia in satellite cell-derived primary myoblasts. Overexpression of Bhlhe40 inhibits Myog expression and mimics the effect of hypoxia on myogenesis. Inhibition of Bhlhe40, conversely, up-regulates Myog expression and promotes myogenic differentiation. Importantly, Bhlhe40 knockdown rescues myogenic differentiation under hypoxia. Mechanistically, Bhlhe40 binds to the proximal E-boxes of the Myog promoter and reduces the binding affinity and transcriptional activity of MyoD on Myog. Interestingly, hypoxia induces Bhlhe40 expression independent of HIF1α but through a novel p53-dependent signaling pathway. Our study establishes a crucial role of Bhlhe40 in mediating the repressive effect of hypoxia on myogenic differentiation and suggests that inhibition of Bhlhe40 or p53 may facilitate muscle regeneration after ischemic injuries.
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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.