EGFL7 ligates ?v?3 integrin to enhance vessel formation
- Authors
- Nikolic, I., Dudvarski Stankovic, N., Bicker, F., Meister, J., Braun, H., Awwad, K., Baumgart, J., Simon, K., Thal, S.C., Patra, C., Harter, P.N., Plate, K.H., Engel, F.B., Dimmeler, S., Eble, J.A., Mittelbronn, M., Schufer, M.K., Jungblut, B., Chavakis, E., Fleming, I., and Schmidt, M.H.
- ID
- ZDB-PUB-130221-18
- Date
- 2013
- Source
- Blood 121(15): 3041-3050 (Journal)
- Registered Authors
- Jungblut, Benno
- Keywords
- none
- MeSH Terms
-
- Phosphorylation/drug effects
- Gene Expression
- Protein Binding
- Integrin alphaVbeta3/genetics
- Integrin alphaVbeta3/metabolism*
- Cell Movement/genetics
- Immunohistochemistry
- RNA Interference
- Endothelial Growth Factors/genetics
- Endothelial Growth Factors/metabolism*
- Endothelial Growth Factors/pharmacology
- Amino Acid Motifs/genetics
- Human Umbilical Vein Endothelial Cells/metabolism*
- Cell Adhesion/genetics
- Infarction, Middle Cerebral Artery/genetics
- Infarction, Middle Cerebral Artery/metabolism
- HEK293 Cells
- Extracellular Matrix/metabolism
- Blood Vessels/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Immunoprecipitation
- Animals
- Humans
- Mice, Nude
- Mice
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/metabolism
- Zebrafish
- PubMed
- 23386126 Full text @ Blood
Angiogenesis, defined as blood vessel formation from a preexisting vasculature, is governed by multiple signal cascades including integrin receptors, in particular integrin αvβ3. Here we identify the endothelial cell (EC)-secreted factor epidermal growth factor-like protein 7 (EGFL7) as a novel specific ligand of integrin αvβ3 thus providing mechanistic insight into its proangiogenic actions in vitro and in vivo. Specifically, EGFL7 attaches to the ECM and by its interaction with integrin αvβ3 increases the motility of EC, which allows EC to move on a sticky underground during vessel remodeling. We provide evidence that the deregulation of EGFL7 in zebrafish embryos leads to a severe integrin-dependent malformation of the caudal venous plexus (CVP), pointing towards the significance of EGFL7 in vessel development. In biopsies of patients with neurological diseases, vascular EGFL7 expression rose with increasing EC proliferation. Further, EGFL7 became upregulated in vessels of the stroke penumbra using a mouse model of reversible middle cerebral artery occlusion (MCAO). Our data suggest that EGFL7 expression depends on the remodeling state of the existing vasculature rather than on the phenotype of neurological disease analyzed. In sum, our work sheds a novel light on the molecular mechanism EGFL7 engages to govern physiological and pathological angiogenesis.