VEGFR-3 ligand-binding and kinase activity are required for lymphangiogenesis but not for angiogenesis.

Abstract:

:Although VEGFR-3 deficiency disrupts blood vascular development during early embryogenesis, the underlying mechanism was not clear. To characterize its function in angiogenesis and lymphangiogenesis, we employed two genetically modified mouse models in this study, targeting the coding region for the ligand-binding domain (Vegfr3(ΔLBD)) or the tyrosine kinase domain with an inactivation point mutation (Vegfr3(TKmut)). We show that lymphatic growth was disrupted in Vegfr3(ΔLBD/ΔLBD) and Vegfr3(TKmut/TKmut) mice, but blood vessels developed normally in both embryo and yolk sac. Interestingly, in Vegfr3(ΔLBD/ΔLBD) but not Vegfr3(TKmut/TKmut) mice, lymph sac was present but there was lack of lymphangiogenic sprouting. We further demonstrate that both the wild-type and mutant forms of VEGFR-3 could form heterodimers with VEGFR-2, and decreased the level of phospho-VEGFR-2 and the downstream phospho-Erk1/2 in endothelial cells when they were treated with VEGF-A. These findings indicate that signaling mediated via VEGFR-3 activation by its cognate ligands (VEGF-C/-D) is not required for angiogenesis, and that VEGFR-3 may play a role in this process by modulating VEGFR-2-mediated signals.

journal_name

Cell Res

journal_title

Cell research

authors

Zhang L,Zhou F,Han W,Shen B,Luo J,Shibuya M,He Y

doi

10.1038/cr.2010.116

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

1319-31

issue

12

eissn

1001-0602

issn

1748-7838

pii

cr2010116

journal_volume

20

pub_type

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