Endothelial Cell Specific Receptor TIE-2 as a Therapeutic Target
Abstract
Angiopoietin-1 (Ang-1) and its receptor Tie-2, a trans-membrane tyrosine kinase uniquely expressed by endothelial cells, are essential to developmental angiogenesis. The phenotypic abnormalities shown by null mutation studies suggest that Tie-2 signaling is necessary for the maintenance and expansion of the primitive capillary network. We present in vitro evidence indicating that the Ang-1/Tie-2 system participates in the regulation of capillary tubule formation and is necessary for the survival of confluent endothelial cells. Although recombinant Ang-1, which induces Tie-2 phosphorylation, has no effect on the proliferation of endothelial cells, treatment of confluent ABAE cells grown on collagen gels with Ang-1 (100 ng/ml) causes the cells to migrate into the collagen gel and form capillary-like tubules. A soluble form of the Tie-2 extra-cellular domain blocks Ang-1 induced tubule-formation. Specific elimination of Tie-2 protein expression in cultured adult bovine aortic endothelial cells (ABAE) as a result of transfection with an antisense oligonucleotide causes cell death in a dose dependent manner (IC50 = 50 nM), with a 6-fold increase in the rate of apoptosis. These findings are consistent with the view that Ang-1/Tie-2 signaling is essential for both angiogenesis and endothelial cell survival.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA382384
Entities
People
- Luyuan Li
Organizations
- Georgetown University