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

• DOI: 10.1084/jem.20062642
• Publication Date: 2007-05-30T01:34:45Z
• Authors: 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
• Keywords: Lymphangiogenesis; Lymphatic vessel; Lymphatic Endothelium

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 pathway triggers VEGFR-3–independent we used both transgenic adenoviral overexpression of placenta factor (PlGF) VEGF-E, are specific activators VEGFR-1 -2, respectively. Unlike PlGF, VEGF-E induced circumferential lymphatic hyperplasia, but essentially no new sprouting, when transduced into mouse skin vectors. This effect was inhibited blocking VEGF-C -D. Postnatal without increased density vessels, detected in mice expressing skin, PlGF. Surprisingly, hyperplasia postnatally, it did rescue loss vessels embryos where VEGF-D were blocked. Our data suggests VEGFR-2 signals promote enlargement, unlike blood involved sprouting generate vivo.