Current Insights into the role of HIF-1 in cutaneous wound healing
Abstract
Hypoxia Inducible Factor-1 (HIF-1) is considered the major coordinator of the cellular adaptive response to hypoxia. Over recent years, its activity in the context of wound healing has been the object of increasing investigation. On the molecular level, HIF-1 transcriptional target products have been shown to regulate the process of endothelial cell survival, migration and proliferation (VEGF, ANGPT-1, ANGPT-2, ANGPT-4, FGF-2, PlGF, PDGF-B, RGC-32), vascular smooth muscle cell migration and proliferation (FGF-2, EGF, PDGF, thrombospondin) and mobilization of Circulating Angiogenic Cells to the periphery (SFD-1/CXCR4). Studies on the effect of HIF-1 on the expression and activity of extracellular cell matrix modifying enzymes, such as MMPs and prolidase, have been conducted in the context of tumor angiogenesis and metastasis, and have resulted in controversial findings. A growing body of evidence suggests that HIF-1 also affects reepithelialization of the wound bed, through increasing keratinocyte migration, but decreasing their proliferation. Diminished HIF-1 levels and activity have been documented in conditions of impaired wound healing, such as wound healing in aged and in diabetic mice. The increasing number of studies on the role of HIF-1 in wound healing, apart from answering certain questions, has also raised an equal number, if not more. Clarifying the topics that still remain unclear could introduce a new era of HIF-1 targeted management of a wide range of problematic wounds.
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Hypoxia may be the single most important event following tissue injury, and adaptation to hypoxic stress via HIF signaling plays a critical role in promoting wound healing.
“Thus, hypoxia may well be viewed as the single most important event following tissue injury, and, indeed, adaptation to hypoxic stress via HIF signaling plays a critical role in promoting wound healing processes [74,75].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [74]
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Influential
- Authors
- Andrikopoulou, E., Zhang, X., Sebastian, R., Marti, G., Liu, L., M. Milner, S., & W. Harmon, J.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Current Molecular Medicine
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2011-04-01
- Volume
- 11
- Issue
- 3
- Pages
- 218-235
- ISSN
- 1566-5240 (ISSN-L)
- OpenAlex
- W2150961929
- Cited by
- 77
- References
- 0
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 8 · 2013: 8 · 2012: 6
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- HIF-1, hypoxia, skin wound healing, angiogenesis, vascular endothelial growth factor, angiopoietins, FGF2, PDGF-B, SDF-1/CXCR4, circulating angiogenic cells, vascular smooth muscle cells, endothelial cells, extracellular matrix, matrix metalloproteinases, prolidase, keratinocyte migration, re-epithelialization, diabetic wound healing, delayed wound healing
- MeSH terms
- Animals, Cell Movement, Extracellular Matrix, Humans, Oxygen, Skin, Wound Healing, Cell Hypoxia, Neovascularization, Physiologic, Mice, Hypoxia-Inducible Factor 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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