Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes.
IMPLICATIONS FOR NORMAL AND IMPAIRED WOUND HEALING (*)
- Stefan Frank(1)(§)(¶),
- Griseldis Hübner(1)(§)(**),
- Georg Breier(2),
- Michael T. Longaker(3),
- David G. Greenhalgh(4) and
- Sabine Werner(1)(§§)
- From the (1) Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried, Germany, the
- (2)Max-Planck-Institut für physiologische und klinische Forschung, Parkstrasse 1, 61231 Bad Nauheim, Germany, the
- (3)Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, New York 10016, and the
- (4)Department of Surgery, Shriners Burns Institute and the University of Cincinnati, Cincinnati, Ohio 45229
- §§ To whom correspondence should be addressed: Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried, Germany. Tel.: 49-89-8578-2269/2271; Fax: 49-89-8578-2814.
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-β1, keratinocyte growth factor, or the proinflammatory cytokine tumor necrosis factor α, 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.
Footnotes
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↵§ These authors have equally contributed to this work.
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↵¶ Supported by a fellowship from the Schering Forschungsgemeinschaft.
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↵** Recipient of a Boehringer Ingelheim fellowship.
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↵* This work was supported by a grant from the Fritz-Thyssen-Stiftung (to S. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- EGF
-
epidermal growth factor
- TGF-β
-
transforming growth factor-β
- TNF-α
-
tumor necrosis factor-α
- VEGF
-
vascular endothelial growth factor
- bp
-
base pair(s)
- DMEM
-
Dulbecco's modified Eagle's medium
- FCS
-
fetal calf serum
- KGF
-
keratinocyte growth factor
- IL
-
interleukin.
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↵2 G. Hübner, unpublished data.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
