Reabsorption in the proximal tubuli-ultrastructural evidence for a novel aspect of renal VEGF trafficking.

Many clinical and experimental studies have revealed VEGF as an important factor in the pathophysiology of renal damage during diabetes mellitus (DM). Anti-VEGF therapy is in clinical use for treatment of DM and other diabetes-related (and unrelated) diseases. Nevertheless, little is known about the metabolism of VEGF in the kidneys. In order to determine the ultrastructural localization of VEGF in the kidney, we study the distribution of VEGF in the kidney of rats by using immunogold immunohistochemistry. Our light-microscopic data showed remarkable re-distribution of VEGF in proximal tubular cells (PTCs) during prolonged hyperglycemia, a DM type 2 model (DM2), which was confirmed by transmission electron microscopy (TEM) findings. TEM findings revealed an initial presence of VEGF in the vesicular transport apparatus of PTCs in healthy rats and its gradual translocation to the apical membrane of PTCs after renal damage caused by high sucrose treatment. The presented data add to our understanding of kidney VEGF trafficking, providing novel insight into the renal metabolism and pharmacodynamics of the cytokine. This could have a high impact on the use of VEGF and anti-VEGF therapy in different renal diseases.