Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting

Maria Wirzenius, Tuomas Tammela, Marko Uutela, Yulong He, Teresa Odorisio, Giovanna Zambruno, Janice A. Nagy, Harold F. Dvorak, Seppo Ylä-Herttuala, Masabumi Shibuya, Kari Alitalo

Research output: Contribution to journalArticlepeer-review

Abstract

Lymphatic vessel growth, or lymphangiogenesis, is regulated by vascular endothelial growth factor-C (VEGF-C) and -D via VEGF receptor 3 (VEGFR-3). Recent studies suggest that VEGF, which does not bind to VEGFR-3, can also induce lymphangiogenesis through unknown mechanisms. To dissect the receptor pathway that triggers VEGFR-3-independent lymphangiogenesis, we used both transgenic and adenoviral overexpression of placenta growth factor (PlGF) and VEGF-E, which are specific activators of VEGFR-1 and -2, respectively. Unlike PlGF, VEGF-E induced circumferential lymphatic vessel hyperplasia, but essentially no new vessel sprouting, when transduced into mouse skin via adenoviral vectors. This effect was not inhibited by blocking VEGF-C and -D. Postnatal lymphatic hyperplasia, without increased density of lymphatic vessels, was also detected in transgenic mice expressing VEGF-E in the skin, but not in mice expressing PlGF. Surprisingly, VEGF-E induced lymphatic hyperplasia postnatally, and it did not rescue the loss of lymphatic vessels in transgenic embryos where VEGF-C and VEGF-D were blocked. Our data suggests that VEGFR-2 signals promote lymphatic vessel enlargement, but unlike in the blood vessels, are not involved in vessel sprouting to generate new lymphatic vessels in vivo. JEM

Original languageEnglish
Pages (from-to)1431-1440
Number of pages10
JournalJournal of Experimental Medicine
Volume204
Issue number6
DOIs
Publication statusPublished - Jun 11 2007

ASJC Scopus subject areas

  • Immunology

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