Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.
Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.
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DOI：
10.1084/jem.180.3.1141
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发表时间：
1994-09-01
期刊：
影响因子：
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通讯作者：
Dvorak HF
中科院分区：
文献类型：
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作者：
Detmar M;Brown LF;Claffey KP;Yeo KT;Kocher O;Jackman RW;Berse B;Dvorak HF
银屑病皮肤的特征是微血管渗透性过高和血管增殖，但其机制尚不清楚。我们在此报告，银屑病皮肤的增生性表皮表达的血管通透性因子（VPF；血管内皮生长因子）数量显着增加，血管通透性因子是一种选择性内皮细胞有丝分裂原，可增强微血管通透性。此外，两种VPF受体kdr和flt-1在乳头状真皮微血管内皮细胞中过度表达。转化生长因子 α (TGF-α) 是一种在银屑病表皮中过度表达的细胞因子，可通过培养的表皮角质形成细胞诱导 VPF 基因表达。 TGF-α刺激的角质形成细胞分泌的VPF具有生物活性，其在体外对真皮微血管内皮细胞的促有丝分裂作用证明了这一点。总之，这些发现表明 TGF-α 通过自分泌机制调节银屑病中的 VPF 表达，导致血管通透性过高和血管生成。类似的机制可能在肿瘤和皮肤伤口愈合中发挥作用，这些伤口也通常表达 VPF 和 TGF-α。
Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular 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 endothelial cells. Transforming growth factor alpha (TGF- alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene 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. Together, these findings suggest that TGF- alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.