title: Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing.
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.
authors.affiliation: Max-Planck-Institut für Biochemie, Martinsried, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Frank
authors.forename: G
authors.initials: G
authors.lastname: Hübner
authors.forename: G
authors.initials: G
authors.lastname: Breier
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
authors.forename: D G
authors.initials: DG
authors.lastname: Greenhalgh
authors.forename: S
authors.initials: S
authors.lastname: Werner
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015603:Keratinocytes / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D016228:Endothelial Growth Factors; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D008222:Lymphokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051523:Fibroblast Growth Factor 7; D016753:Interleukin-10; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor