Loss of epidermal hypoxia-inducible factor-1α accelerates epidermal aging and affects re-epithelialization in human and mouse
Abstract
In mouse and human skin, HIF-1α is constitutively expressed in the epidermis, mainly in the basal layer. HIF-1α has been shown to have crucial systemic functions: regulation of kidney erythropoietin production in mice with constitutive HIF-1α epidermal deletion, and hypervascularity following epidermal HIF-1α overexpression. However, its local role in keratinocyte physiology has not been clearly defined. To address the function of HIF-1α in the epidermis, we used the mouse model of HIF-1α knockout targeted to keratinocytes (K14-Cre/Hif1aflox/flox). These mice had a delayed skin phenotype characterized by skin atrophy and pruritic inflammation, partly mediated by basement membrane disturbances involving laminin-332 (Ln-332) and integrins. We also investigated the relevance of results of studies in mice to human skin using reconstructed epidermis and showed that HIF-1α knockdown in human keratinocytes impairs the formation of a viable reconstructed epidermis. A diminution of keratinocyte growth potential, following HIF-1α silencing, was associated with a decreased expression of Ln-322 and α6 integrin and β1 integrin. Overall, these results indicate a role of HIF-1α in skin homeostasis especially during epidermal aging.
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Because the epidermis is not directly supplied with blood, in vivo oxygen levels range between 0.5% and 8%.
“Because the epidermis is not directly supplied with blood, in vivo oxygen levels range between 0.5% and 8%.63,64”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [64]
Culturing FibHSEs at 3% O2 mimics endogenous oxygen conditions.
“we cultured FibHSEs for 14 days at 3% O2 to mimic endogenous oxygen conditions.63,64”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [64]
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BackgroundActivation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
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DAMPs, ageing, and cancer: The ‘DAMP Hypothesis’
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Single-cell transcriptomics of human-skin-equivalent organoids
Stabell, A. R., Lee, G. E., Jia, Y., Wong, K. N., Wang, S., Ling, J., Nguyen, S. D., Sen, G. L., Nie, Q., & Atwood, S. X. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112511 · Cited by 30 · see citing works
- Authors
- Rezvani, H. R., Ali, N., Serrano-Sanchez, M., Dubus, P., Varon, C., Ged, C., Pain, C., Cario-André, M., Seneschal, J., Taïeb, A., de Verneuil, H., & Mazurier, F.
- Affiliations
- Université de Bordeaux (FR)
- INSERM, Biothérapies des maladies génétiques et cancers, U1035, 146 rue Léo Saignat, Bordeaux, F-33000 France
- Corresponding author
- Mazurier, Frédéric
- ORCID
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2011-12-15
- Volume
- 124
- Issue
- 24
- Pages
- 4172-4183
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2053595480
- Cited by
- 90
- References
- 7
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 11 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 11 · 2014: 6 · 2013: 3 · 2012: 1
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- hypoxia-inducible factor-1α, keratinocytes, skin homeostasis, re-epithelialization, laminin-5, integrins, basement membrane, skin atrophy, reconstructed epidermis, keratinocyte growth
- MeSH terms
- Kalinin, Aging, Animals, Epidermis, Humans, Phenotype, Skin, Wound Healing, Down-Regulation, Keratinocytes, Cell Adhesion Molecules, Integrins, Apoptosis, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Gene Knockout Techniques, Cell Cycle Checkpoints
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