Twp Treatment Of Mesangial Proliferative Glomerulonephritis In Vivo Molecular Mechanism

[Background/Aims] Multi-glycoside from Tripterygium wilfordii Hook. f. (GTW) is used for various immune and inflammatory diseases including renal diseases represented by mesangial proliferative glomerulonephritis (MsPGN) in China. However, there have been no fundamental studies on the operating mechanism of GTW on MsPGN. The aim of this study is to examine as the first step the effects of GTW on acute injurious process such as mesangial injury and proteinuria in an acute and reversible Thy.1.1 glomerulonephritis (Thy 1.1 GN) model and then to clarify the action mechanism of GTW at molecular level by examining its effects on various injurious factors in this model. [Methods] Thy1.1 GN was induced in rats by a single intravenous injection with 500μg of anti-Thy1. mAb 1-22-3. Daily oral administration of GTW and vehicle as a control was started from 3 days before injection of mAb to the day of sacrifice in each experiment. Fourteen rats were randomly divided into 2 groups, the GTW-treated group and vehicle treated group, and sacrificed on day 14 in Experiment 1 or on day 7 in Experiment 2 after induction of Thy1.1 GN. Proteinuria was determined on days 1, 3, 5, 7, 10, and 14 in Experiment 1 or on 1, 3, 5, and 7 in Experiment 2. From blood and kidneys taken at sacrifice, blood biochemical parameters, mesangial morphological changes, glomerular macrophage infiltration, and glomerular mRNA expression of cytokines were examined. [Results] In Experiment 1, proteinuria and mesangial matrix expansion were significantly attenuated by GTW treatment. In Experiment 2, GTW treatment significantly ameliorated proteinuria, mesangial lesions and macrophage accumulation in glomerulus. In addition, it significantly reduced the glomerular expression of mRNA for PDGF, MCP-1, and IL-2. [Conclusion] GTW ameliorated not only proteinuria but also mesangial alterations in Thy1.1 GN most likely by reducing expression of injurious cytokines, indicating that GTW has suppressive effects on acute inflammatory changes in glomeruli.