Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing.
Open accessAbstract
Persistent microvascular hyperpermeability to plasma proteins even after the cessation of injury is a characteristic but poorly understood feature of normal wound healing. It results in extravasation of fibrinogen that clots to form fibrin, which serves as a provisional matrix and promotes angiogenesis and scar formation. We present evidence indicating that vascular permeability factor (VPF; also known as vascular endothelial growth factor) may be responsible for the hyperpermeable state, as well as the angiogenesis, that are characteristic of healing wounds. Hyperpermeable blood vessels were identified in healing split-thickness guinea pig and rat punch biopsy skin wounds by their capacity to extravasate circulating macromolecular tracers (colloidal carbon, fluoresceinated dextran). Vascular permeability was maximal at 2-3 d, but persisted as late as 7 d after wounding. Leaky vessels were found initially at the wound edges and later in the subepidermal granulation tissue as keratinocytes migrated to cover the denuded wound surface. Angiogenesis was also prominent within this 7-d interval. In situ hybridization revealed that greatly increased amounts of VPF mRNA were expressed by keratinocytes, initially those at the wound edge, and, at later intervals, keratinocytes that migrated to cover the wound surface; occasional mononuclear cells also expressed VPF mRNA. Secreted VPF was detected by immunofluoroassay of medium from cultured human keratinocytes. These data identify keratinocytes as an important source of VPF gene transcript and protein, correlate VPF expression with persistent vascular hyperpermeability and angiogenesis, and suggest that VPF is an important cytokine in wound healing.
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VEGF is a cytokine released by macrophages and keratinocytes during wound reconstruction to promote angiogenesis.
“Vascular endothelial growth factor, or VEGF, is a cytokine released by macrophages and keratinocytes during wound reconstruction to promote angiogenesis.195–197”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [196]
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- Authors
- Brown, L. F., Yeo, K. T., Berse, B., Yeo, T. K., Senger, D. R., Dvorak, H. F., & van de Water, L.
- Affiliations
- Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.
- ORCID
- Berse, B
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1992-11-01
- Volume
- 176
- Issue
- 5
- Pages
- 1375-1379
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2119412
- OpenAlex
- W1971248512
- Cited by
- 878
- References
- 21
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 22 · 2022: 20 · 2021: 24 · 2020: 23 · 2019: 30 · 2018: 19 · 2017: 27 · 2016: 18 · 2015: 18 · 2014: 23 · 2013: 25 · 2012: 29
- FWCI
- 25.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca043967-07, 5r01ca028471-13)
- National Cancer Institute (CA-43967, CA 50453, CA-28471, R01CA050453)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- vascular endothelial growth factor, wound healing, keratinocytes, angiogenesis, microvascular hyperpermeability, plasma extravasation, fibrin, granulation tissue, VEGF mRNA expression, cytokines
- MeSH terms
- Animals, Base Sequence, Cells, Cultured, Female, Guinea Pigs, Humans, Lymphokines, Molecular Sequence Data, RNA, Messenger, Wound Healing, Keratinocytes, Endothelial Growth Factors, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Rats
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