Kuroda K, Sapadin A, Shoji T, Fleischmajer R, Lebwohl M
Department of Dermatology, Mount Sinai School of Medicine, New York, New York, USA.
J Invest Dermatol. 2001 May;116(5):713-20. doi: 10.1046/j.1523-1747.2001.01316.x.
Psoriasis is a chronic inflammatory skin disease in which epidermal proliferation is closely associated with excessive microvascular expansion within the papillary dermis. Angiopoietins have recently been identified as the major ligands of the endothelial- specific receptor Tie2. Angiopoietin 1 induces Tie2 signaling as a receptor activator and maintains blood vessel formation, whereas angiopoietin 2 destabilizes vessels by blocking Tie2 signaling as an antagonist of angiopoietin 1 and acts with vascular endothelial growth factor to initiate angiogenesis. In this study we examined the potential role of angiopoietins and the Tie2 receptor in vascular changes of psoriasis. Angiopoietin 1, angiopoietin 2, and Tie2 were upregulated in involved psoriasis skin compared to uninvolved psoriasis skin, healthy skin, and chronic spongiotic dermatitis skin. Angiopoietin 1 was expressed by stromal cells in the highly vascularized papillary dermis of involved psoriasis skin. Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor. Vascular endothelial growth factor and basic fibroblast growth factor, which were overexpressed in involved psoriasis skin, enhanced angiopoietin 2 and Tie2 expression in dermal microvascular endothelial cell cultures. Thus, our findings suggest that upregulation of angiopoietin 1, angiopoietin 2, and Tie2 is closely associated with the development of microvascular proliferation in psoriasis, and that the angiopoietin-Tie2 system may act coordinately with vascular endothelial growth factor and basic fibroblast growth factor to promote neovascularization in psoriasis. Moreover, successful antipsoriatic treatment was accompanied by noticeable reduction of angiopoietin 2 expression, suggesting that alteration of angiopoietin 2 expression may be particularly important in controlling vascular proliferation in the treatment of psoriasis.
银屑病是一种慢性炎症性皮肤病，其中表皮增殖与乳头真皮内过度的微血管扩张密切相关。血管生成素最近被确定为内皮特异性受体Tie2的主要配体。血管生成素1作为受体激活剂诱导Tie2信号传导并维持血管形成，而血管生成素2作为血管生成素1的拮抗剂通过阻断Tie2信号传导使血管不稳定，并与血管内皮生长因子共同作用以启动血管生成。在本研究中，我们研究了血管生成素和Tie2受体在银屑病血管变化中的潜在作用。与未受累的银屑病皮肤、健康皮肤和慢性海绵状皮炎皮肤相比，受累的银屑病皮肤中血管生成素1、血管生成素2和Tie2上调。血管生成素1由受累的银屑病皮肤中高度血管化的乳头真皮中的基质细胞表达。血管生成素2由增殖表皮附近的内皮细胞表达，该表皮大量表达血管内皮生长因子。在受累的银屑病皮肤中过表达的血管内皮生长因子和碱性成纤维细胞生长因子增强了真皮微血管内皮细胞培养物中血管生成素2和Tie2的表达。因此，我们的研究结果表明，血管生成素1、血管生成素2和Tie2的上调与银屑病微血管增殖的发展密切相关，并且血管生成素-Tie2系统可能与血管内皮生长因子和碱性成纤维细胞生长因子协同作用以促进银屑病中的新生血管形成。此外，成功的抗银屑病治疗伴随着血管生成素2表达的显著降低，这表明血管生成素2表达的改变在控制银屑病治疗中的血管增殖方面可能特别重要。
