Podocyte-Specific Expression of Angiopoietin-2 Causes Proteinuria and Apoptosis of Glomerular Endothelia

• DOI: 10.1681/asn.2006101093
• Publication Date: 2007-07-12T01:30:31Z
• Authors: Belinda Davis; Alessandra Dei Cas; David A. Long; Kathryn E. White; Anthea Hayward; Ching-Hsin Ku; Adrian S. Woolf; Rudolf Bilous; Giancarlo Viberti; Luigi Gnudi
• Keywords: Nephrin; Angiopoietin; Albuminuria; Angiopoietin receptor

Angiopoietin-2 (Ang-2) modulates embryonic vascular differentiation primarily by inhibiting the antiapoptotic effects of Ang-1 on endothelia that express Tie-2 receptor. Ang-2 is transiently expressed developing glomeruli but downregulated with normal maturation. Glomerular expression is, however, markedly upregulated in animal models diabetic nephropathy and glomerulonephritis, both leading causes human chronic renal disease, affecting 10% world population. It was hypothesized might have significant roles pathobiology glomerular disease. Mice inducible podocyte-specific overexpression were generated. When transgene induced adults for up to 10 wk, mice had increases albuminuria endothelial apoptosis, decreases growth factor-A nephrin proteins, critical maintenance filtration barrier functional integrity, respectively. There was, no change systemic BP, creatinine clearance, or markers fibrosis, podocytes appeared structurally intact. In kidneys young animals which been during organogenesis, increased apoptosis occurred just-formed glomeruli. vitro, short-term exposure isolated wild-type murine exogenous led decreased levels protein. These novel results provide insight into molecular mechanisms underlying proteinuric disorders, highlight potentially complex interactions between subsets cells, emphasize how a factor has development may be harmful when re-expressed context adult