Foxn1 expression in keratinocytes is stimulated by hypoxia: further evidence of its role in skin wound healing
Open accessAbstract
Recent studies have shown that the transcription factor Foxn1, which is expressed in keratinocytes, is involved in the skin wound healing process, yet how Foxn1 functions remains largely unknown. Our latest data indicate that Foxn1 drives skin healing via engagement in re-epithelization and the epithelial-mesenchymal transition (EMT) process. In the present study, 2D-DIGE proteomic profiling analysis of in vitro cultured keratinocytes transfected with adenoviral vector carrying Foxn1-GFP or GFP alone (control) revealed forty proteins with differential abundance between the compared groups. Among the proteins with Foxn1-dependent expression, several enable adaptation to hypoxia. Subsequent experiments revealed that hypoxic conditions (1% O 2) stimulate endogenous and exogenous (transfected Ad-Foxn1) Foxn1 expression in cultured keratinocytes. A proteomics analysis also identified proteins that can act as a factors controlling the balance between cell proliferation, differentiation and apoptosis in response to Foxn1. We also showed that in C57BL/6 keratinocytes, the stimulation of Foxn1 by hypoxia is accompanied by increases in Mmp-9 expression. These data corroborate the detected co-localization of Foxn1 and Mmp-9 expression in vivo in post-wounding skin samples of Foxn1::Egfp transgenic mice. Together, our data indicate that Foxn1 orchestrates cellular changes in keratinocytes in both physiological (self-renewal) and pathological (skin wound healing) contexts.
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The 34 genes in the hypoxia gene module have been experimentally shown to be upregulated in response to hypoxia and/or possess a hypoxia response element in the promoter region.
“a manually curated list of 34 genes that have been experimentally shown to be upregulated in response to hypoxia and/or possess a hypoxia response element in the promoter region59–62”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [59]
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- Authors
- Kur-Piotrowska, A., Bukowska, J., Kopcewicz, M. M., Dietrich, M., Nynca, J., Slowinska, M., & Gawronska-Kozak, B.
- Affiliations
- InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences (PL)
- Venue
- Scientific Reports
- Published
- 2018-04-03
- Volume
- 8
- Issue
- 1
- Pages
- 5425-5425
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5882803
- OpenAlex
- W2795840452
- Cited by
- 26
- References
- 52
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 2 · 2014: 1
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- State University of New York
- SUNY Downstate Medical Center
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- Foxn1, keratinocytes, hypoxia, skin wound healing, re-epithelialization, epithelial-mesenchymal transition, MMP-9, transcription factors, proteomic profiling, cell proliferation and differentiation, apoptosis, transgenic mice
- MeSH terms
- Animals, Cell Differentiation, Gene Expression Regulation, Skin, Wound Healing, Keratinocytes, Cell Hypoxia, Matrix Metalloproteinase 9, Proteomics, Mice, Forkhead Transcription Factors
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