Effect Of Leflunomide On WT1 Expression In Rat With Masugi Nephritis

Objective:To investigate the role of immunocomplex and WT1(Wilms'tumor1)in the pathogenesis of Masugi nephritis and the effect of novelimmunosuppressive agents, leflunomide(LEF) on Masugi nephritis inrats.Methods and Results:1. Anti-GBM antiserum was prepared by immunizing rabbits with thesolution of rats' GBM. Next, Masugi nephritis was induced by injectionof rabbit-anti-rat GBM antibody into tail veins.2. Proteinuria of the nephritis and the control rats were measured withBCA protein assay kit. In the nephritis groups, proteinuria wassignificantly higher than the controls. There was crescent formation andthe GBM was thickening In the nephritis groups.3. By immunofluorescence, the rat GBM IgG and WT1 protein levelsin renal tissue were compared between the Masugi nephritis groups andthe controls. In the nephritis group, the rat IgG level of GBMsignificant increased compared with the controls. But the level of WT1protein in renal tissue in the nephritis group was decreased compared ofthat in normal control group. 4. Proteinuria in LEF-treated nephritis rats was significantly lowerthan that in non-treated nephritis rats. The fluorescence intensity of IgGin kidney is decreased in LEF-treated nephritis rats compared withnon-treated nephritis rats. The fluorescence intensity of WT1 in kidneywas increased in LEF-treated ones than the non-treated ones. InLEF-treated nephritis rats, the protein expression of WT1 in kidneyshowed remarkable increasing compared with non-treated nephritis rats.Conclusion:1. There are distinct differences in the IgG deposition and the moleculeof WT1 in rat glomeruli during Masugi nephritis. The remarkablechanges of Immune complex deposition and the expression of protein ofWT1 are closely associated with the development of proteinuria inMasugi nephritis rats.2. LEF reduce the proteinuria in Masugi nephritis rats. LEF haveeffects on anti-GBM nephritis through reducing immune complexdeposition and increasing molecules of podocytes. Further studies areneeded to determine the role of LEF in Masugi nephritis.