MOLECULAR REGULATION OF UVB-INDUCED CUTANEOUS ANGIOGENESIS

We determined whether cutaneous angiogenesis induced by exposure of mi ce to ultraviolet-B (WB) radiation is associated with an imbalance bet ween positive and negative angiogenesis-regulating molecules. Unshaved C3H/HeN mice were exposed to a single dose (15 kJ per m(2)) of UVB, A t various times, the mice were killed, and their external ears were pr ocessed for routine histology and immunohistochemistry. Antibodies aga inst proliferating cell nuclear antigen and bromodeoxyuridine identifi ed dividing cells. Antibodies against CD31/PECAM-1 identified endothel ial cells, and antibodies against basic fibroblast growth factor (bFGF ), vascular endothelial growth factor/vascular permeability factor, an d interferon-beta (IFN-beta) identified angiogenesis-regulating molecu les. Epidermal hyperplasia was documented by 48 h and reached a maximu m on day 7 after exposure to WB, The expression of bFGF increased by 2 4 h, whereas the expression of IFN-beta decreased by 72 h after exposu re to WB, The expression of vascular endothelial growth factor/vascula r permeability factor increased slightly after irradiation. The altere d balance between bFGF and IFN-beta was associated with increased endo thelial cell proliferation (bromodeoxyuridine + CD31 + cells) within e xisting blood vessels, leading to telangiectasia and new blood vessels . UV-induced epidermal hyperplasia and cutaneous angiogenesis were hig hest in IFN-alpha/beta receptor knockout mice. These results demonstra te that in response to UVB radiation, dividing keratinocytes produce a positive angiogenic molecule (bFGF) but not a negative angiogenic mol ecule (IFN-beta), and that this altered balance is associated with enh anced cutaneous angiogenesis.