Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins

被引：1072

作者：

Karkkainen, MJ

Haiko, P

Sainio, K

Partanen, J

Taipale, J

Petrova, TV

Jeltsch, M

Jackson, DG

Talikka, M

Rauvala, H

Betsholtz, C

Alitalo, K

机构：

[1] Univ Helsinki, Mol Canc Biol Lab, FIN-00014 Helsinki, Finland

[2] Univ Helsinki, Haartman Inst, Ludwig Inst Canc Res, FIN-00014 Helsinki, Finland

[3] Univ Helsinki, Univ Helsinki Hosp, Biomedicum Helsinki, FIN-00014 Helsinki, Finland

[4] Biomedicum Helsinki, Inst Biomed Dev Biol, Helsinki 00029, Finland

[5] HUCH Diagnost, Helsinki 00029, Finland

[6] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland

[7] John Radcliffe Hosp, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DU, England

[8] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland

[9] Univ Gothenburg, Dept Biochem Med, S-40530 Gothenburg, Sweden

来源：

NATURE IMMUNOLOGY | 2004年 / 5卷 / 01期

关键词：

D O I：

10.1038/ni1013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：74 / 80

页数：7

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