OVEREXPRESSION OF VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL GROWTH-FACTOR AND ITS RECEPTORS IN PSORIASIS

Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We re port here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vas cular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors , kdr and flt-1, are overexpressed by papillary dermal microvascular e ndothelial cells. Transforming growth factor alpha (TGF-alpha), a cyto kine that is also overexpressed in psoriatic epidermis, induced VPF ge ne expression by cultured epidermal keratinocytes. VPF secreted by TGF -alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. T ogether, these findings suggest that TGF-alpha regulates VPF expressio n in psoriasis by an autocrine mechanism, leading to vascular hyperper meability and angiogenesis. Similar mechanisms may operate in tumors a nd in healing skin wounds which also commonly express both VPF and TGF -alpha.