We show that in vivo podocyte VEGF-A regulates fibronectin and alphaVbeta3 integrin signaling in the glomerulus, and that disruption of VEGFR2- alphaVbeta3 integrin crosstalk by acute podocyte VEGF knockdown damages the three layers of the glomerular filtration barrier, resulting in proteinuria and acute renal failure. The gene discussed is VEGFA; the disease is acute kidney injury.