Nature cell biology, 2011-10, Vol.13 (10), p.1202
2011
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- Autor(en) / Beteiligte
- Titel
- VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling
- Ist Teil von
- Nature cell biology, 2011-10, Vol.13 (10), p.1202
- Ort / Verlag
- England
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Angiogenesis, the growth of new blood vessels, involves specification of endothelial cells to tip cells and stalk cells, which is controlled by Notch signalling, whereas vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 have been implicated in angiogenic sprouting. Surprisingly, we found that endothelial deletion of Vegfr3, but not VEGFR-3-blocking antibodies, postnatally led to excessive angiogenic sprouting and branching, and decreased the level of Notch signalling, indicating that VEGFR-3 possesses passive and active signalling modalities. Furthermore, macrophages expressing the VEGFR-3 and VEGFR-2 ligand VEGF-C localized to vessel branch points, and Vegfc heterozygous mice exhibited inefficient angiogenesis characterized by decreased vascular branching. FoxC2 is a known regulator of Notch ligand and target gene expression, and Foxc2(+/-);Vegfr3(+/-) compound heterozygosity recapitulated homozygous loss of Vegfr3. These results indicate that macrophage-derived VEGF-C activates VEGFR-3 in tip cells to reinforce Notch signalling, which contributes to the phenotypic conversion of endothelial cells at fusion points of vessel sprouts.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1476-4679DOI: 10.1038/ncb2331Titel-ID: cdi_pubmed_primary_21909098
- Format
- –
- Schlagworte
- Animals, Antibodies - pharmacology, Cell Line, Tumor, Endothelial Cells - drug effects, Endothelial Cells - metabolism, Forkhead Transcription Factors - genetics, Forkhead Transcription Factors - metabolism, Gene Expression Regulation, Human Umbilical Vein Endothelial Cells - metabolism, Humans, Macrophages - metabolism, Mice, Mice, Knockout, Neovascularization, Pathologic - genetics, Neovascularization, Pathologic - metabolism, Neovascularization, Physiologic - drug effects, Phosphatidylinositol 3-Kinase - metabolism, Protein Kinase Inhibitors - pharmacology, Receptors, Notch - antagonists & inhibitors, Receptors, Notch - metabolism, Retinal Vessels - metabolism, Rhombencephalon - blood supply, RNA Interference, Signal Transduction - drug effects, Time Factors, Transduction, Genetic, Transfection, Vascular Endothelial Growth Factor A - genetics, Vascular Endothelial Growth Factor A - metabolism, Vascular Endothelial Growth Factor B - genetics, Vascular Endothelial Growth Factor B - metabolism, Vascular Endothelial Growth Factor C - genetics, Vascular Endothelial Growth Factor C - metabolism, Vascular Endothelial Growth Factor D - genetics, Vascular Endothelial Growth Factor D - metabolism, Vascular Endothelial Growth Factor Receptor-3 - deficiency, Vascular Endothelial Growth Factor Receptor-3 - genetics, Vascular Endothelial Growth Factor Receptor-3 - metabolism