Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis
Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis
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DOI：
10.1182/blood-2002-12-3793
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发表时间：
2003-07-01
期刊：
影响因子：
20.3
通讯作者：
Rudge, JS
中科院分区：
文献类型：
--
作者：
Xia, YP;Li, BS;Rudge, JS
目前正在考虑使用血管内皮生长因子(VEGF)来促进治疗性血管生成的基因治疗方法，用于治疗从缺血性心脏病到无法愈合的皮肤溃疡等各种疾病。在这里，我们进行了令人惊讶的观察：转基因血管内皮生长因子转移到皮肤导致了严重的炎症皮肤状况，具有银屑病的许多细胞和分子特征，包括特征性的血管变化、表皮变化和炎症浸润物。在这个模型中，即使是长期存在的银屑病也仍然依赖于转基因的血管内皮生长因子，因为它可以通过添加强大的血管内皮生长因子拮抗剂血管内皮生长因子陷阱有效地逆转。以前通过转基因传递表皮角质形成细胞生长因子或炎症介质来忠实复制牛皮癣表型的尝试产生的表型与人类牛皮癣只有部分相似之处，留下了关于这种疾病的病因的未解问题。转基因血管内皮生长因子诱导牛皮癣样表型的能力表明了一种治疗这种疾病的新的病因和治疗方法，并进一步证实了人们对可能与输送血管内皮生长因子的治疗尝试有关的可能的促炎不良反应的担忧。(C)2003年，由美国血液病学会提供。
Gene therapy approaches involving vascular endothelial growth factor (VEGF) to promote therapeutic angiogenesis are under consideration for conditions ranging from ischemic heart disease to nonhealing skin ulcers. Here we make the surprising observation that the transgenic delivery of VEGF to the skin results in a profound inflammatory skin condition with many of the cellular and molecular features of psoriasis, including the characteristic vascular changes, epidermal alterations, and inflammatory infiltrates. Even longstanding psoriatic disease remains dependent on the transgenic VEGF in this model because it can be effectively reversed by the addition of VEGF Trap, a potent VEGF antagonist. Previous attempts to faithfully replicate the psoriatic phenotype through the transgenic delivery of epidermal keratinocyte growth factors or inflammatory mediators generated phenotypes with only partial resemblance to human psoriasis, leaving unanswered questions about the etiology of this disease. The ability of transgenic VEGF to induce a psoriasiform phenotype suggests a new etiology and treatment approach for this disease and further substantiates emerging concerns about possible proinflammatory adverse effects that might be associated with therapeutic attempts to deliver VEGF. (C) 2003 by The American Society of Hematology.