Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin
Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin
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DOI：
10.1161/01.res.88.6.623
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发表时间：
2001-03-30
影响因子：
20.1
通讯作者：
Alitalo, K
中科院分区：
文献类型：
--
作者：
Enholm, B;Karpanen, T;Alitalo, K
血液和淋巴血管的生长部分是由血管内皮生长因子（VEGF）家族分泌的多肽介导的。原型VEGF结合VEGF受体(VEGFR)-1和VEGFR-2并产生血管生成，而VEGF- c结合VEGFR-2和VECFR-3，在不同的实验中要么是血管生成，要么是淋巴管生成。我们使用腺病毒基因转移方法来比较这些生长因子在成年小鼠中的作用。将编码人VEGF- c或VEGF的重组腺病毒皮下注射到C57B16小鼠或裸鼠耳内。免疫组化分析显示，VEGF- c在注射后4天上调VEGFR-2和VEGFR-3的表达，VEGF上调VEGFR-2的表达。2周后，组织化学和免疫组织化学分析，包括淋巴血管内皮透明质酸受体-1 （LYVE-1）、血管内皮标志物血小板内皮细胞粘附分子-1 （PECAM-1）和增殖细胞核抗原（PCNA）的染色显示，VEGF- c主要诱导淋巴管生成，而VEGF仅诱导血管生成。这些结果对利用这些生长因子进行基因治疗的规划具有重要意义。
The growth of blood and lymphatic vasculature is mediated in part by secreted polypeptides of the vascular endothelial growth factor (VEGF) family. The prototype VEGF binds VEGF receptor (VEGFR)-1 and VEGFR-2 and is angiogenic, whereas VEGF-C, which binds to VEGFR-2 and VECFR-3, is either angiogenic or lymphangiogenic in different assays. We used an adenoviral gene transfer approach to compare the effects of these growth factors in adult mice. Recombinant adenoviruses encoding human VEGF-C or VEGF were injected subcutaneously into C57B16 mice or into the ears of nude mice. Immunohistochemical analysis showed that VEGF-C upregulated VEGFR-2 and VEGFR-3 expression and VEGF upregulated VEGFR-2 expression at 4 days after injection. After 2 weeks, histochemical and immunohistochemical analysis, including staining for the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the vascular endothelial marker platelet-endothelial cell adhesion molecule-1 (PECAM-1), and the proliferating cell nuclear antigen (PCNA) revealed that VEGF-C induced mainly lymphangiogenesis in contrast to VEGF, which induced only angiogenesis. These results have significant implications in the planning of gene therapy using these growth factors.