Cited by 764Wound Healing and TreatmentsAngiogenesis and VEGF in CancerLymphatic System and Diseases

Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes.

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Frank, Stefan, Hübner, Griseldis, Breier, Georg, Longaker, Michael T., Greenhalgh, David G., Werner, Sabine·1995·Journal of Biological Chemistry

Abstract

Recent in situ hybridization studies had demonstrated a strong increase in vascular endothelial growth factor (VEGF) mRNA expression in the hyperproliferative epithelium during wound healing. To determine potential mediators of VEGF induction during this process, we analyzed the regulation of VEGF expression in cultured human keratinocytes. We found a large induction of VEGF expression upon treatment of quiescent cells with serum, epidermal growth factor, transforming growth factor-beta 1, keratinocyte growth factor, or the proinflammatory cytokine tumor necrosis factor alpha, respectively. Since all these factors are present at the wound site during the early phase of wound healing, they might also be responsible for VEGF induction after cutaneous injury. To determine the importance of increased VEGF production for wound repair, we compared the time course of VEGF mRNA expression during wound healing of healthy control mice with the kinetics of VEGF expression during skin repair of genetically diabetic db/db mice which are characterized by impaired wound healing. In normal mice we found elevated VEGF mRNA levels during the period when granulation tissue formation occurs. In contrast, VEGF mRNA levels even declined during this period in db/db mice, suggesting that a defect in VEGF regulation might be associated with wound healing disorders.

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Crossref · 10.1074/jbc.270.21.12607

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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”

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Cites

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Research works printed but not linked: 10

  1. Clark, R. A. F. (1991) in Physiology, Biochemistry, and Molecular Biology ofthe Skin (Goldsmith, L. A., ed) pp. 576-601, Oxford University Press, Oxford
  2. Roberts, A. B., Sporn, M. B., Assoian, R. K, Smith, J. M., Roche, N. S., Wakefield, L. M., Heine, U. L, Liotta, L. A., Falanga, V. Kehrl, J. H., and Fauci, A. S. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 4167-4171
  3. Frater-Schroder, M., Risau, W., Hallmann, R., Gautschi, P., and Bohlen, P. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 5277-5281
  4. Gospodarowicz, D., Abraham, J. A., and Schilling, J. (1989) Proc. Natl. Acad. Sci. U. S. A. 86,7311-7315
  5. Peters, K. G., deVries, C., and Williams, L. T. (1993) Proc. Nat!. Acad. Sci.
  6. Werner, S., Peters, K. G., Longaker, M. T., Fuller-Pace, F., Banda, M., and Williams, L. T. (1992) Proc. Natl. Acad. Sci. U. S. A. 89,6896-6900
  7. Rubin, J. S., Osada, H., Finch, P. W., Taylor, W. G., Rudikoff, S., and Aaronson, S. A. (1989) Proc. Nat!. Acad. Sci. U. S. A. 86,802-806
  8. Grossman, R. M., Krueger, J., Yourish, D., Granelli-Piperno, A., Murphy, D. P., May, L. T., Kupper, T. S., Sehgal, P. B., and Gottlieb, A. B. (1989) Proc. Nat!. Acad. Sci. U. S. A. 86, 6367-6371
  9. Dinarello, C. A. (1991) in The Cytokine Handbook (Thomson, A. W., ed) pp. 47-82, Academic Press, New York
  10. Wong, H. L., and Wahl, S. M. (1989) in Human Monocytes (Zembala, M., and Asherson, G. L., ed) pp. 383-394, Academic Press, New York

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Authors
Frank, S., Hübner, G., Breier, G., Longaker, M. T., Greenhalgh, D. G., & Werner, S.
Affiliations
  • Max Planck Institute of Biochemistry (DE)
  • Max Planck Society (DE)
  • NYU Langone Health (US)
  • University of Cincinnati (US)
Corresponding author
Werner, Sabine
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1995-05
Volume
270
Issue
21
Pages
12607-12613
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1550364580
Cited by
764
References
48
Citations by year
2026: 4 · 2025: 11 · 2024: 18 · 2023: 21 · 2022: 22 · 2021: 18 · 2020: 14 · 2019: 17 · 2018: 23 · 2017: 16 · 2016: 16 · 2015: 34 · 2014: 23 · 2013: 18 · 2012: 24
FWCI
45.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
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 › Oncology › Lymphatic System and Diseases
Keywords
vascular endothelial growth factor, keratinocytes, wound healing, VEGF mRNA expression, epidermal growth factor, TGF-β1, keratinocyte growth factor, TNF-α, diabetic wound healing, db/db mice, granulation tissue, skin wounds
MeSH terms
Animals, Cells, Cultured, Diabetes Mellitus, Dose-Response Relationship, Drug, Epidermal Growth Factor, Fibroblast Growth Factors, Gene Expression Regulation, Growth Substances, Lymphokines, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, RNA, Messenger, Tumor Necrosis Factor-alpha, Wound Healing, Keratinocytes, Endothelial Growth Factors, Interleukin-10, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice, Fibroblast Growth Factor 7, Fibroblast Growth Factor 10

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