Cell-autonomous requirement for β1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice
2008
β1 integrin (encoded by Itgb1 ) is established as a regulator
of angiogenesis based upon the phenotypes of complete knockouts of β1
heterodimer partners or ligands and upon antibody inhibition studies in mice.
Its direct function in endothelial cells (ECs) in vivo has not been determined
because Itgb1 -/- embryos die before vascular development.
Excision of Itgb1 from ECs and a subset of hematopoietic cells, using
Tie2-Cre , resulted in abnormal vascular development by embryonic day
(e) 8.5 and lethality by e10.5. Tie1-Cre mediated a more restricted
excision of Itgb1 from ECs and hematopoietic cells and resulted in
embryonic lethal vascular defects by e11.5. Capillaries of the yolk sacs were
disorganized, and the endothelium of major blood vessels and of the heart was
frequently discontinuous in mutant embryos. We also found similar vascular
morphogenesis defects characterized by EC disorganization in embryonic
explants and isolated ECs. Itgb1 -null ECs were deficient in adhesion
and migration in a ligand-specific fashion, with impaired responses to laminin
and collagens, but not to fibronectin. Deletion of Itgb1 reduced EC
survival, but did not affect proliferation. Our findings demonstrate thatβ
1 integrin is essential for EC adhesion, migration and survival during
angiogenesis, and further validate that therapies targeting β1 integrins
may effectively impair neovascularization.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
45
References
120
Citations
NaN
KQI