Podocyte-specific VEGF down-regulation and pathophysiological development.

It is well-known that vascular endothelial growth factor (VEGF) plays a key role in development and pathology, but its function in normal adult tissues is rarely understood. Increased use of anti-angiogenic therapies targeting VEGF in human pathologies have shown more and more adverse effects. In this report, a conditional expression model (Tet-On system) was used to down-regulate podocyte VEGF in adult mice, which resulted in many kidney problems, characterized by glomerular morphological changes, proteinuria, reduced water consumption and urination, increased urine electro-conductivity, as well as high susceptibility to BSA stress. Our findings indicated that podocyte-specific VEGF down-regulation resulted in poor kidney performance and led mice to be more susceptible to further kidney damages.