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

Abstract

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. 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. 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. 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. 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.