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• W2305890380 abstract "[F-FC090] Inducible Overexpression of Angiopoietin-1 in Podocytes Results in Albuminuria and Foot Process Effacement in Mice.Luigi Gnudi, Alessandra Dei Cas, Kathrin E. White, Anthea Hayward, David A. Long, Adrian S. Woolf, Rudolf Bilous, Belinda Davis, Sally Marshall, Giancarlo Viberti Cardiovascular Division, Kings College London, London, United Kingdom; Department of Diabetes and Metabolism, Newcastle University, Newcastle, United Kingdom; Nephro-Urology Unit, Institute of Child Health, UCL, London, United KingdomThe angiopoietins (Ang) are a family of secreted growth factors which play a role in blood vessel injury and repair. In the glomeruli, Ang-1 is expressed in the podocytes and it has been suggested that a finely regulated Ang-1/Ang-2 ratio contributes towards the integrity of the glomerular filtration barrier. To understand this process we overexpressed Ang-1 in podocytes of normal mice.Podocyte-specific overexpression of Ang-1 and -galactosidase cDNA was obtained using the Tet-On regulatable inducible system using the podocyte-specific promoter podocin. Mice were studied at 8-10 weeks of age. To activate the transgene, Doxycycline (DOX)(2mg/mL) was administered with water for up to 10 weeks. The following groups of mice were studied: transgenic (TG) with DOX, TG without DOX, controls (C) with DOX, and C without DOX.Kidney cortex was collected for subsequent analysis for -galactosidase staining, western immunoblotting, immunohistochemistry, and electron microscopy (EM) studies. Albuminuria was determined by ELISA in 24h collections.Podocyte -galactosidase staining was present only in TG-DOX treated animals, indicating absence of leaky transgene activity. Western immunoblottting showed a 2-3 fold increase in Ang-1 protein overexpression in the DOX treated TG mice only (p<0.05). Albuminuria was increased by 2-3 fold in the TG-DOX treated mice (p<0.05) as early as 5 weeks. At 10 weeks VEGF expression was upregulated by 70% (p<0.05) but no changes in nephrin expression was observed. By EM, significant foot process effacement/fusion was detected in Ang-1 overexpressing glomeruli (p<0.05).We have generated a transgenic mouse model of podocyte-specific inducible Ang-1 overexpression. This resulted in albuminuria, upregulation of VEGF, and podocyte foot processes effacement, demonstrating that excess local Ang-1 perturbs glomerular barrier function." @default.
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• W2305890380 date "2007-10-01" @default.
• W2305890380 modified "2023-09-27" @default.
• W2305890380 title "Inducible overexpression of angiopoietin-1 in podocytes results in albuminuria and foot process effacement in mice" @default.
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