Angiopoietin growth factors and Tie receptor tyrosine kinases in renal vascular development

Angiopoietin-1 (Ang-1) is a secreted growth factor which binds to and activ ates the Tie-2 receptor tyrosine kinase. The factor enhances endothelial ce ll survival and capillary morphogenesis, and also limits capillary permeabi lity. Ang-2 binds the same receptor but fails to activate it: hence, it is a natural inhibitor of Ang-1. Ang-2 destabilises capillary integrity, facil itating sprouting when ambient vascular endothelial growth factor (VEGF) le vels are high, but causing vessel regression when VEGF levels are low. Tie- 1 is a Tie-2 homologue but its ligands are unknown. Angiopoietin and Tie ge nes are expressed in the mammalian metanephros, the precursor of the adult kidney, where they may play a role in endothelial precursor growth. Tie-1-e xpressing cells can be detected in the metanephros when it first forms and, based on transplantation experiments, these precursors contribute to the g eneration of glomerular capillaries. During glomerular maturation, podocyte -derived Ang-1 and mesangial-cell-derived Ang-2 may affect growth of nascen t capillaries. After birth, vasa rectae acquire their mature configuration and Ang-a expressed by descending limbs of loops of Henle would be well pla ced to affect the growth of this medullary microcirculation. Finally, preli minary data implicate angiopoietins in deregulated vessel growth in Wilms' kidney rumours and in vascular remodelling after nephrotoxicity.