PUBLICATION
Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization
- Authors
- Kawamura, H., Li, X., Goishi, K., van Meeteren, L.A., Jakobsson, L., Cebe-Suarez, S., Shimizu, A., Edholm, D., Ballmer-Hofer, K., Kjellen, L., Klagsbrun, M., and Claesson-Welsh, L.
- ID
- ZDB-PUB-080801-13
- Date
- 2008
- Source
- Blood 112(9): 3638-3649 (Journal)
- Registered Authors
- Goishi, Katsutoshi, Li, Xiajuan
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Embryonic Stem Cells/cytology
- Embryonic Stem Cells/drug effects
- Embryonic Stem Cells/metabolism
- Endothelial Cells/cytology
- Endothelial Cells/drug effects*
- Endothelial Cells/metabolism*
- Enzyme Activation/drug effects
- Humans
- Ligands
- Mice
- Models, Biological
- Neovascularization, Physiologic
- Neuropilin-1/genetics
- Neuropilin-1/metabolism*
- Pericytes/cytology
- Pericytes/drug effects
- Pericytes/metabolism
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism
- Signal Transduction
- Swine
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Vascular Endothelial Growth Factor A/pharmacology*
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Zebrafish
- p38 Mitogen-Activated Protein Kinases/metabolism*
- PubMed
- 18664627 Full text @ Blood
Citation
Kawamura, H., Li, X., Goishi, K., van Meeteren, L.A., Jakobsson, L., Cebe-Suarez, S., Shimizu, A., Edholm, D., Ballmer-Hofer, K., Kjellen, L., Klagsbrun, M., and Claesson-Welsh, L. (2008) Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization. Blood. 112(9):3638-3649.
Abstract
Vascular endothelial growth factor (VEGF)-A regulates vascular development and angiogenesis. VEGF isoforms differ in ability to bind coreceptors heparan sulfate (HS) and neuropilin-1 (NRP1). We used VEGF-A165 (which binds HS and NRP1), VEGF-A121 (binds neither HS nor NRP1) and parapoxvirus VEGF-E-NZ2 (binds NRP1 but not HS) to investigate the role of NRP1 in organization of endothelial cells into vascular structures. All three ligands induced similar level of VEGFR-2 tyrosine phosphorylation in the presence of NRP1. In contrast, sprouting angiogenesis in differentiating embryonic stem cells (embryoid bodies), formation of branching pericyte-embedded vessels in subcutaneous matrigel plugs and sprouting of intersegmental vessels in developing zebrafish was induced by VEGF-A165 and VEGF-E-NZ2 but not by VEGF-A121. Analyses of recombinant factor with NRP1-binding gain- and loss-of function properties, supported the conclusion that NRP1 is critical for VEGF-induced sprouting and branching of endothelial cells. Signal transduction antibody arrays implicated NRP1 in VEGF-induced activation of p38MAPK. Inclusion of the p38MAPK inhibitor SB203580 in VEGF-A165-containing matrigel plugs led to attenuated angiogenesis and poor association with pericytes. Our data strongly indicate that the ability of VEGF ligands to bind NRP1 influences p38MAPK activation, and formation of functional, pericyte-associated vessels.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping