Suppression of glomerular injury by enhancing a VEGF signaling to its endothelial cells

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We studied effects of VEGF on glomerular endothelial injury and its repair. Thy1 glomerulonephritis (Thy1 GN) was * in the rat by intraperitoneal injection of 0.125 to 0.15μg of a monoclonal antibody (OX7) to an adult Wistar rat. Ten μg per dose of human recombinant VEGF165 was injected intraperitoneally to the rat at 4 hours before injecting OX7 and 1, 2 and 3 days after the injection. As a control, BSA was injected instead of the VEGF.Kidneys were harvested at 24hours, 4 days and 18 days after injecting the OX7 and tissues were studied histologically. Changes of glomerular mesangial, endothelial, and epithelial cells were examined by immunohistochemistry using anti-Thy1, anti-vWF and anti-PECUM, and anti-p250 antibodies, respectively. Mitotic changes of the cells were evaluated by staining PCNA.At 24 hours after injecting OX7, mesangiolysis and ballooning of capillaries were observed and VEGF suppressed the latter and significantly preserved the glomerular structure. At 4 days after the injection, a repair of injured glomeruli including proliferations of mesangial and endothelial cells were observed by administrating VEGF.Contrarily, no repair was observed in the control. After 18 days, repair was almost finished in glomeruli of the VEGF-administered rats. In the control, mesangial proliferation was observed and repair was proceeding. These results show that recombinant VEGF165 protects glomerular capillaries and promotes the repair of injured glomeruli. Remained structures of the capillry may be used as a scaffold for mesangial proliferation and a mitotic stimulation of VEGF to endothelial cells may promote the glomerular repair. Although further studies are needed, enhancing VEGF signaling may be useful in the treatment of human glomerulonephritis associated with endothelial injuries