期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 20, 期 2, 页码 239-244出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2008020243
关键词
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资金
- Kids Kidney Research, Biotechnology and Biologic Sciences Research Council [S 13745]
- European Foundation
- Kidney Research UK [SF1/2008] Funding Source: researchfish
Angiopoietins 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, down-regulated 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.
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