Vascular endothelial growth factor-A (VEGF) is required for endothelial cell differentiation and survival. To investigate the renoprotective properties of VEGF in diabetes an inducible Cre-loxP gene targeting system was used to excise VEGF from podocytes of adult mice (VEGFKO). Diabetes was induced by streptozotocin (STZ) at 2.5 weeks of age and VEGFKO was induced by doxycycline (dox) at 3-4 weeks of age. Blood and urine were collected weekly to monitor for hyperglycaemia and proteinuria, respectively. Mice were dissected 8 weeks after diabetes induction or earlier if morbidly ill; twenty percent of the mice in the DM+VEGFKO group died before the surrogate endpoint. Glomerular VEGF mRNA expression was decreased in VEGFKO mice compared to controls. However, DM+VEGFKO mice had significantly greater proteinuria, degrees of glomerular sclerosis, and glomerular cell apoptosis. These results confirm that VEGF is normally upregulated in diabetes but reducing VEGF expression in diabetes causes severe kidney injury.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/29625 |
| Date | 25 August 2011 |
| Creators | Sivaskandarajah, Gavasker |
| Contributors | Quaggin, Susan E. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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