Overexpression of the angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase in psoriatic epidermis

Abstract

Considerable evidence indicates that the microvascular changes observed in psoriasis are a result of angiogenesis. Vascular proliferation is driven by the local production of molecules which have angiogenic activity. Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PDECGF/TP) is a potent angiogenic factor active in in vivo angiogenesis assays and overexpressed in several tumour types. We have demonstrated by ribonuclease protection analysis a consistently high degree of PDECGF/TP mRNA production in lesional psoriatic skin, while immunohistochemical studies revealed strong PDECGF/TP immunoreactivity in lesional epidermis, with nuclear staining present in basal keratinocytes and cytoplasmic immunoreactivity in suprabasal layers. Non-lesional skin showed minimal PDECGF/TP mRNA production and weak epidermal immunostaining. These results indicate a potential role for PDECGF/TP in the pathophysiology of psoriasis, and reveal a target for antiangiogenesis therapy in the treatment of this disease.

Comano's (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: A potential mechanism of its anti-psoriatic action

“…Further lines of evidence that we are presently gathering show that in vitro exposure to CW-DMEM also interferes with the increased expression and secretion of at least two more angiogenic cytokines, IL-1 and IL-6 (9,(12)(13)(14)(15)(16)(17)(18)(19), on the part of human psoriatic keratinocytes (unpublished data). Conceivably, such complex anti-angiogenic effects brought about by CW balneotherapy would justify, from a pathophysiological standpoint, at least part of its known beneficial effects on the clinical manifestations of psoriasis (59), and concurrently rule out the possibility that such benefits are of the placebo kind.…”

“…neutrophils, T lymphocytes, monocytes) (4,5), it has been surmised that psoriasis is an angioproliferative ailment depending upon the release of angiogenic molecules by the epidermis (6)(7)(8)(9)(10)(11). Increased amounts of several angiogenic cytokines, including transforming growth factor-· (TGF-·), tumour necrosis factor-· (TNF-·), interleukin-1 (IL-1), IL-6, IL-20, amphiregulin, plateletderived endothelial cell growth factor/thymidine phosphorylase (TP), endothelial cell stimulating angiogenesis factor (ESAF), and VEGF-A are produced and secreted by the psoriatic keratinocytes (9,(12)(13)(14)(15)(16)(17)(18)(19).…”

Multisubstrate adduct inhibitors: Drug design and biological tools

“…Over-expression of TPase has also been implicated in inflammatory disease states including rheumatoid arthritis and psoriasis 124,125 . TPase catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose 1-phosphate 126 .…”

Cytokine profile in psoriatic arthritis: search for relationships with inflammation and blood rheological properties

“…Полагают, что при ПсА механизм ангиогенеза запуска-ется довольно рано, на субклиниче-ской стадии «пре-артрита» [14], и ре-гулируется такими цитокинами, как ФНО α, СЭФР, ангиопоэтин 1 и 2 (АНП 1 и 2), трансформирующий фактор роста β (ТФР β). В перива-скулярных областях кожи и синовии отмечается повышенное содержание данных цитокинов, что может быть связано с хронической гипоксией в зонах воспаления [15][16][17].…”