Analysis of glomerular VEGF mRNA and protein expression in murine mesangioproliferative glomerulonephritis

Abstract

Capillary repair is crucial in the healing of glomerulonephritis (GN). The vascular endothelial growth factor (VEGF) has pro-angiogenic properties and plays an important role in glomerular capillary regeneration. Habu Snake Venom (HSV) GN, a murine model for mesangioproliferative GN, was induced in uninephrectomized C57/BL6 mice. Glomerular damage and capillary repair were assessed using morphometry, stereology, and confocal laser scanning microscopy. Mesangiolytic glomeruli were microdissected (days 1,3,7,14) using laser capture microdissection technique. VEGF mRNA expression was analyzed by real-time polymerase chain reaction and compared to intact glomeruli of healthy controls. Spatiotemporal VEGF gene and protein expression was determined using nonradioactive in situ hybridization and immunohistochemistry. On day 1, diseased animals developed focal mesangiolysis paralleled by a significant decrease in length density of glomerular capillaries that gradually returned to baseline levels thereafter, indicating capillary growth in response to initial injury. Glomerular VEGF mRNA expression increased on day 3 and returned back to baseline and beyond at day 14 when the glomerular recovery process was completed. Similarly, glomerular VEGF protein expression tended to be higher on day 3. The present study documents temporarily increased glomerular VEGF gene and protein expression during the healing of HSV GN, suggesting a potential role of VEGF in the repair of mesangiolytic glomerular damage.