Participation of endothelial cells in the development of glomerulosclerosis: a study on murine serum sickness nephritis with mitomycin C.

To investigate the participation of endothelial cells in glomerulosclerosis, the study was performed in serum sickness nephritis (SSN) with administration of mitomycin C (MMC). SSN was induced in 8 week male Fisher rats by sensitizing them with albumin, chicken egg (EA). Then MMC (0.5 mg/kg bodyweight) was injected daily for 3 days and they were killed at 1, 2, 4 and 6 week intervals. Significant mesangial expansion and sclerosis were observed in the experimental mixed SSN-MMC group in comparison to the SSN or MMC control group from 1 week to 6 weeks (P < 0.05). Moreover at 1 week, double contour appearance of the glomerular capillary wall, basement membrane splitting and disruption were observed light microscopically in the mixed SSN-MMC group. Electron microscopy revealed peripheral capillary basement membrane disruption with huge subepithelial, mesangial osmiophilic deposits and epithelial foot process effacement. At 6 weeks, disappearance of the endothelial cell fenestration and subepithelial basement membrane-like material formation were observed in the MMC group. Based on these results, it is suggested that MMC induced assault on the glomerular endothelial cell produces prominent glomerular capillary basement membrane disruption at the early phase of SSN, resulting in the accumulation of huge subepithelial and mesangial deposits, mesangial cell proliferation, production of the extracelluar matrix component and initiation of glomerulosclerosis.