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lüll Roles of angiopoietins in kidney development and disease Woolf AS; Gnudi L; Long DAJ Am Soc Nephrol 2009[Feb]; 20 (2): 239-44Angiopoietins are a family of growth factors, the best studied being angiopoietin 1 (Ang-1), which binds to and tyrosine-phosphorylates endothelial Tie-2, causing enhanced survival and cell-cell stabilization. Ang-2 and Tie-1 downregulate Ang-1-induced Tie-2 signaling, and angiopoietin actions are further modified by vascular endothelial growth factor A and integrins. Metanephric capillaries express Tie genes, whereas metanephric mesenchyme, maturing tubules, and mature podocytes express Ang-1. Ang-1 null embryos begin to form blood vessels, but subsequent vascular remodeling fails, and analyses of chimeric wild-type/Tie null mutant embryos show that Tie genes are needed for renal endothelial survival. Ang-2 is transiently expressed in renal arterial smooth muscle and mesangial cells, and tubules around adult vasa rectae express Ang-2. Ang-2 null mice have increased pericytes around kidney cortical peritubular capillaries, perhaps an indirect consequence of upregulated Tie-2 signaling. Ang-1 therapies attenuate peritubular capillary loss in adult models of tubulointerstitial disease, although, in one study, this was accompanied by enhanced inflammation and fibrosis. Podocyte-directed Ang-2 transgenic overexpression causes glomerular endothelial apoptosis, downregulated nephrin expression, and increased albuminuria, and glomerular Ang-2 is upregulated in hyperglycemic and immune-mediated glomerulopathies. Thus, angiopoietins affect podocyte as well as glomerular endothelial biology, and imbalanced angiopoietin signaling contributes to glomerular pathobiology.|*Gene Expression Regulation[MESH]|Angiopoietin-2/genetics/metabolism[MESH]|Angiopoietins/*physiology[MESH]|Animals[MESH]|Apoptosis[MESH]|Cell Survival[MESH]|Humans[MESH]|Kidney Diseases/*metabolism[MESH]|Kidney Glomerulus/metabolism[MESH]|Kidney/*metabolism[MESH]|Mice[MESH]|Models, Biological[MESH]|Signal Transduction[MESH]|Transgenes[MESH] |