Vascular Endothelial Growth Factor is Augmented in the Kidney with Chronic Partial Ureteral Obstruction and Further Stimulated by Lipopolysaccharide

Abstract

Vascular endothelial growth factor (VEGF), a critical mitogen for angiogensis, has been shown to be activated in the inflammatory process of fibrotic lung disease and inflammatory arthritis. In the present study we examined the expression of VEGF in Sprague‐Dawley rats subject to chronic partial ureteral obstruction (PUO) for 30 days to produce renal interstitial fibrosis. To create PUO, the right kidney was removed and the left ureter diverted into the psoas muscles. A sham operation was performed in the control group. In an additional group of PUO, the inflammatory response was augmented by intraperitoneal injection of lipopolysaccharide (LPS) (1 mg/kg BW) 24 hr before removal of the left kidney to examine renal histology and VEGF expression by immunoblot and RT‐PCR analyses. In PUO rats intense inflammation and tubulointerstitial fibrosis were seen on histology examination. Immunoblot analysis showed that VEGF/b‐actin in the renal cortex was 10.1±1.1 (mean±SD) (densitometry units) in 8 PUO rats, greater than 5.3±0.7 in the 8 sham‐operated rats (p<0.05), and increased further to 12.5±2.7 in 8 PUO rats receiving LPS (p<0.05). VEGF/b‐actin in the medulla of the PUO kidney was 9.6±1.8, greater than 5.5±1.2 in the sham‐operated rats (p<0.05) and increased to 13.1±1.6 in PUO rats receiving LPS (p<0.05). VEGF mRNA expression in the cortex increased by over two‐fold (2.17±0.28, p<0.03) in PUO rats compared with sham‐operated rats and increased further in PUO rats receiving LPS (fold change of 3.14±0.29, p<0.01 vs PUO). VEGF mRNA expression in the medulla increased by 3.15±0.43 in PUO rats compared with sham‐operated rats (p<0.03) and increased further by 5.09±0.47 in PUO rats receiving LPS (p<0.03 vs PUO). These results show that VEGF expression is augmented in chronic obstructed kidney and further stimulated by LPS, suggesting that it participates in chronic renal tubulointerstitial fibrosis.