Regulation of vascular endothelial growth factor expression in cultured keratinocytes: Implications for normal and impaired wound healing

Stefan Frank, Griseldis Hübner, Georg Breier, Michael T. Longaker, David G Greenhalgh, Sabine Werner

Research output: Contribution to journalArticle

626 Scopus citations

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 a, 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.

Original languageEnglish (US)
Pages (from-to)12607-12613
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number21
StatePublished - May 26 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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