Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins
Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins
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DOI：
10.1038/ni1013
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发表时间：
2004-01-01
影响因子：
30.5
通讯作者：
Alitalo, K
中科院分区：
文献类型：
--
作者：
Karkkainen, MJ;Haiko, P;Alitalo, K
淋巴管对于免疫监视、组织液稳态和脂肪吸收是必不可少的。淋巴管形成或功能缺陷引起水肿。在这里，我们表明，血管内皮生长因子C（VEGF-C）是所需的淋巴发育的初始步骤。在Vegfc（-/-）小鼠中，内皮细胞定向于淋巴系，但不发芽形成淋巴管。发芽被VEGF-C和VEGF-D拯救，但不被VEGF拯救，表明VEGF受体3特异性。由于组织中的液体积聚，淋巴管的缺乏导致产前死亡，并且Vegfc（+/-）小鼠发展为皮肤淋巴发育不全和水肿。我们的研究结果表明，VEGF-C是淋巴管生成所必需的旁分泌因子，并表明这两个Vegfc等位基因是正常淋巴发育所必需的。
Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc(-/-) mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc(+/-) mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development.