HIF modulation of Wnt signaling regulates skeletal myogenesis in vivo
Open accessAbstract
Deeper insight into the molecular pathways that orchestrate skeletal myogenesis should enhance our understanding of, and ability to treat, human skeletal muscle disease. It is now widely appreciated that nutrients, such as molecular oxygen (O2), modulate skeletal muscle formation. During early stages of development and regeneration, skeletal muscle progenitors reside in low O2 environments before local blood vessels and differentiated muscle form. Moreover, low O2 availability (hypoxia) impedes progenitor-dependent myogenesis in vitro through multiple mechanisms, including activation of hypoxia inducible factor 1α (HIF1α). However, whether HIF1α regulates skeletal myogenesis in vivo is not known. Here, we explored the role of HIF1α during murine skeletal muscle development and regeneration. Our results demonstrate that HIF1α is dispensable during embryonic and fetal myogenesis. However, HIF1α negatively regulates adult muscle regeneration after ischemic injury, implying that it coordinates adult myogenesis with nutrient availability in vivo. Analyses of Hif1a mutant muscle and Hif1a-depleted muscle progenitors further suggest that HIF1α represses myogenesis through inhibition of canonical Wnt signaling. Our data provide the first evidence that HIF1α regulates skeletal myogenesis in vivo and establish a novel link between HIF and Wnt signaling in this context.
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In C2C12 myoblasts, HIF-1α inhibits the canonical Wnt signaling known to promote muscle regeneration.
“In C2C12 myoblasts, HIF-1α inhibits the canonical Wnt signaling known to promote muscle regeneration [74].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [74]
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Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380 · see citing works
Self-citationHypoxia requires Notch signaling to maintain the undifferentiated cell state
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Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting
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“In C2C12 myoblasts, HIF-1α inhibits the canonical Wnt signaling known to promote muscle regeneration [74].”
BackgroundChaillou1, T., & Lanner, J. T. (2016) · The FASEB Journal · doi:10.1096/fj.201600757r · Cited by 84 · see citing works
- Authors
- Majmundar, A. J., Lee, D. S. M., Skuli, N., Mesquita, R. C., Kim, M. N., Yodh, A. G., Nguyen-McCarty, M., Li, B., & Simon, M. C.
- Affiliations
- Abramson Cancer Center (US)
- Howard Hughes Medical Institute (US)
- Inserm (FR)
- University of Pennsylvania (US)
- Sun Yat-sen University (CN)
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2015-01-01
- Volume
- 142
- Issue
- 14
- Pages
- 2405-12
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC4510864
- OpenAlex
- W2172375221
- Cited by
- 67
- References
- 4
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 3
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (5R01-HL-066310, R01HL066310)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR053461)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- HIF-1α, hypoxia, Wnt signaling, skeletal myogenesis, skeletal muscle regeneration, ischemic injury, muscle progenitors, embryonic myogenesis, oxygen availability, skeletal muscle development
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Immunohistochemistry, Ischemia, Mice, Inbred C57BL, Microscopy, Fluorescence, Mutation, Oxygen, Perfusion, Regeneration, Gene Deletion, Muscle, Skeletal, Gene Expression Regulation, Developmental, Muscle Development, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Wnt Signaling Pathway
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