Vascular endothelial growth factor promotes sensitivity to ultraviolet B-induced cutaneous photodamage.
Acute ultraviolet B (UVB) irradiation of the skin results in erythema, vasodilation, edema, and angiogenesis, which is associated with the expression of vascular endothelial growth factor (VEGF) by epidermal keratinocytes. It is unclear, however, whether VEGF is required for the damage or repair process that occurs in the skin on UVB exposure. We subjected transgenic mice that overexpress VEGF, and their wild-type littermates, to graded doses of acute UVB irradiation. The skin of VEGF-overexpressing mice was highly photosensitive and became erythematic when exposed to half the UVB dose required to induce erythema in wild-type mice. Erythema was associated with proliferating dermal endothelial cells, cutaneous edema, and inflammatory cell infiltration. When subjected to 10 weeks of low-level UVB irradiation, no major changes were observed in wild-type mice, whereas VEGF transgenic mice developed skin damage associated with degradation of the dermal matrix and enhanced vascularization. Systemic treatment with an anti-VEGF blocking antibody reduced the sensitivity of wild-type mice to acute UVB irradiation without inhibiting post-UVB repair. Our results reveal that VEGF promotes the cutaneous damage that occurs after UVB exposure and that the VEGF signaling pathway might serve as a novel target for the prevention of UVB-induced photodamage.
Hirakawa
Satoshi
S
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Fujii
Seishiro
S
Kajiya
Kentaro
K
Yano
Kiichiro
K
Detmar
Michael
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004487:Edema / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004890:Erythema / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010787:Photosensitivity Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D014664:Vasodilation / Q000235:genetics / Q000528:radiation effects*
D000911:Antibodies, Monoclonal; D042461:Vascular Endothelial Growth Factor A