Autocrine VEGF–VEGF-R loop on podocytes during glomerulonephritis in humans

Background. Vascular endothelial growth factor (VEGF) is the most important and tightly regulated angiogenic cytokine in the kidney. Its activity is critical for capillary/glomerular preservation and repair, and recent studies have also demonstrated its relevance for the preservation of podocytes. Methods. The present study investigated a large number (n = 153) of renal biopsies from patients with glomerulonephritis (GN) and evaluated the expression and activity of the glomerular VEGF system [VEGF, VEGF-R1, VEGF-R2 and biologically active VEGF as identified by VEGF–VEGF receptor complexes (VEGF-VEGF-R)] in parallel with markers of renal function, injury and repair. Results. Whereas glomerular VEGF expression was clearly elevated, VEGF-R expression levels were widely unchanged. In parallel to the overall VEGF expression, the biological activity of VEGF on its receptors was uniformly significantly enhanced. Interestingly, the expression pattern of VEGF-R1 and VEGF-R2 significantly changed during GN where a very prominent podocytic pattern appeared, which was also detected for receptor-bound VEGF. VEGF expression and activity could be linked with indicators of renal injury such as glomerular proliferation and creatinine, respectively. Conclusions. This study shows, for the first time, increased podocytic VEGF–VEGF-R binding during human GN, suggesting not only the existence of a glomerular paracrine proangiogenic, but also an autocrine role of the VEGF–VEGF-R system in diseased podocytes.