Vesalius Research Centre, VIB, B-3000 Leuven, Belgium.
J Pathol. 2009 Nov;219(3):356-64. doi: 10.1002/path.2605.
Vascular endothelial growth factor-D (VEGF-D) is one of the two ligands of the VEGFR-3 receptor on lymphatic endothelial cells. Gene-silencing studies in mice and Xenopus tadpoles recently showed that the role of endogenous VEGF-D in lymphatic development is moderate. By contrast, exogenous VEGF-D is capable of stimulating lymphangiogenesis. Nonetheless, its endogenous role in pathological conditions remains largely unknown. Hence, we reassessed its role in disease, using Vegf-d(null) mice. Vegf-d(null) mice were generated that, under physiological conditions, displayed normal embryonic and postnatal lymphangiogenesis and lymphatic remodelling, efficient lymphatic functioning and normal health. Vegf-d(null) mice also reponded normally in models of skin wound healing and healing of infarcted myocardium, despite enhanced expression of VEGF-D in these models in wild-type mice. In contrast, Vegf-d(null) mice displayed reduced peritumoral lymphangiogenesis and lymph node metastasis in an orthotopic pancreatic tumour model. Together, our data indicate that endogenous VEGF-D in mice is dispensible for lymphangiogenesis during development, in postnatal and adult physiology and in several pathological conditions, but significantly contributes to lymphatic metastasis.
血管内皮生长因子-D（VEGF-D）是淋巴管内皮细胞上 VEGFR-3 受体的两个配体之一。最近在小鼠和非洲爪蟾幼体中的基因沉默研究表明，内源性 VEGF-D 在淋巴管发育中的作用是适度的。相比之下，外源性 VEGF-D 能够刺激淋巴管生成。然而，其在病理性条件下的内源性作用在很大程度上仍然未知。因此，我们使用 Vegf-d(null) 小鼠重新评估了其在疾病中的作用。生成了 Vegf-d(null) 小鼠，在生理条件下，它们显示出正常的胚胎和出生后淋巴管生成和淋巴管重塑、有效的淋巴管功能和正常的健康状况。在皮肤伤口愈合和梗死心肌愈合的模型中，尽管野生型小鼠中这些模型中 VEGF-D 的表达增强，但 Vegf-d(null) 小鼠也正常应答。相比之下，在原位胰腺肿瘤模型中，Vegf-d(null) 小鼠显示出肿瘤周围淋巴管生成和淋巴结转移减少。总之，我们的数据表明，内源性 VEGF-D 在小鼠中对于发育过程中的淋巴管生成、出生后和成年生理以及几种病理性条件是可有可无的，但对淋巴管转移有显著贡献。
