Vascular endothelial growth factor causally contributes to the angiogenic response upon ultraviolet B irradiation in vivo

Br J Dermatol. 2002 Apr;146(4):581-7. doi: 10.1046/j.1365-2133.2002.04669.x.

Abstract

Background: Ultraviolet (UV)-B irradiation has been shown to be an inducer of vascular endothelial growth factor (VEGF) in primary keratinocytes and epidermal cell lines in vitro.

Objectives: To determine the expression pattern and the causal role of VEGF in the UVB-mediated angiogenic response in vivo in human skin and in a mouse model.

Methods: Skin biopsies or epidermal lysates thereof were studied for VEGF expression following UVB irradiation at a dose of 50 or 60 mJ cm-2, respectively, using immunostaining and a VEGF-specific highly sensitive sandwich enzyme-linked immunosorbent assay. The VEGF-dependent increase in vessels upon repetitive UVB irradiation was studied in skh-1 hairless mice using immunostaining for factor VIII-related antigen (FVIII RAG) in the presence and absence of intraperitoneally injected neutralizing VEGF antibodies.

Results: VEGF was found to be induced in the epidermis following UVB irradiation of human and mouse skin. Repetitive UVB irradiation of skh-1 hairless mice resulted in an increase in FVIII RAG positive vessels in the skin. UVB-induced angiogenic response could be partly abrogated by neutralizing antibodies against VEGF, while isotype-matched IgG control antibodies did not reveal any suppressive effect.

Conclusions: Our results support previous in vitro data and show the in vivo relevance of VEGF as a paracrine inducer of cutaneous vessels after UVB irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Radiation
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / metabolism*
  • Epidermis / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymphokines / immunology
  • Lymphokines / metabolism*
  • Male
  • Mice
  • Mice, Hairless
  • Neovascularization, Pathologic / metabolism*
  • Radiation Injuries / metabolism*
  • Skin / blood supply*
  • Skin / metabolism
  • Skin / radiation effects*
  • Ultraviolet Rays*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • von Willebrand Factor / metabolism

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • von Willebrand Factor