The anti-oxidative role of glutathione s-transferase mu 2 in anti-GBM induced glomerulonephritis by inhibiting inflammation and oxidative stress (P5121)

Abstract

Abstract Oxidative stress is a common manifestation in chronic inflammation and closely associated with autoimmune diseases. Impaired balance between oxidative stress and antioxidant systems exhibits an important impact on pathogenesis of immune-mediated nephritis. Using anti-GBM induced nephritis mouse model, we have identified a group of redox related genes dysregulated in mouse kidney upon anti-GBM antibody challenge. In this study, we investigated the anti-oxidative effect of glutathione s-transferase mu 2 (Gstm2) on immune-mediated nephritis. Human GSTM2 gene was transduced into mesenchymal stem cell (MSC) and hGSTM2-MSCs were injected to anti-GBM antibody challenged 129/svj mice. Mouse blood urea nitrogen (BUN) and proteinuria were measured to evaluate renal function change and renal histopathological changes were appraised. We found the Gstm2 could alleviate the renal inflammatory damage by suppressing expression of inflammatory chemokines, CCL2, IL1β and IL6 to reduce macrophage and T lymphocyte infiltration. Gstm2 improved renal function by reducing BUN and proteinuria. Moreover, hGSTM2-MSCs significantly reduced the apoptosis of tubular cell by regulating the expression of anti-apoptotic genes (BCL2 and CD40LG) and hGSTM2-MSCs resisted oxidative stress by increasing the expression of catalase and glutathione peroxidase 1. In summary, Gstm2 exhibits protective effect on immune-mediated nephritis by inhibiting inflammatory damage and oxidative stress during inflammatory process.