Description |
The Angiopoietins are a family of growth factors which bind to the endothelial receptor tyrosine kinase Tie2. Two of the Angs, Ang-1 and Ang-4, activate the Tie2 receptor, whereas Ang-2 and Ang-3 inhibit Ang-1-induced Tie2 phosphorylation. Ang-1 is a secreted growth factor which enhances endothelial cell survival and capillary morphogenesis, also it limits capillary permeability. Ang-2 is a natural inhibitor of Ang-1 because it binds the same receptor but fails to activate it. When ambient levels of VEGF are high Ang-2 destabilizes capillary integrity, facilitating sprouting, but when VEGF levels are low it causes vessel regression. Tie-1 is a Tie-2 homologue but its ligands are unknown. Angiopoietin and Tie genes are expressed in the mammalian metanephros, the precursor of the adult kidney, where they may play a role in endothelial precursor growth. Tie-1-expressing cells can be detected in the metanephros when it first forms and, based on transplantation experiments, these precursers contribute to the generation of glomerular capillaries. During glomerular maturation, podocyte derived Ang-1 and mesangial cell derived Ang-2 may affect growth of nacent capillaries. After birth, vasa rectae aquire their mature configuration and Ang-2 expressed by decending limbs of loops of Henle would be well placed to affect the growth of this medullary microcirculation. Preliminary data suggests angiopoietins are implicated in deregulated vessel growth in Wilms' kidney tumors and in vascular remodeling after nephrotoxicity. Existing data suggests that during vascular development VEGF-A and Angiopoietins not only have different roles, but also complementary and coordinated roles. Recombinant Human Angiopoitin-2 (Ang-2) consists of a C-terminal His tagged glycoprotein starting at N-terminal aa residue D68 of the precursor protein. |