Oxidation resistance 1 attenuated lupus nephritis by suppressing oxidative stress and inflammation in kidney (P5119)

Abstract

Abstract Oxidation resistance 1 (Oxr1) was identified to be up-regulated in mouse kidney upon anti-GBM antibody challenge and may play a role in anti-GBM disease and lupus nephritis. Since Oxr1 has been shown to confer resistance against oxidative stress by detoxify reactive oxygen species (ROS), we speculate that Oxr1 may have protective effect against oxidative stress induced renal damage. Thus, we utilized mesenchymal stem cells (MSCs) as vehicles to deliver Oxr1 into the injured kidneys of lupus nephritis model mice and investigated the influence of Oxr1 on glomerulonephritis. Human OXR1 gene was transfected into mouse bone marrow-derived MSCs via lentiviral vector pCDH to establish a stable hOXR1-MSC cell line. 106 hOXR1-MSCs were injected (i.v.) into B6.Sle1.Sle2.Sle3 lupus mice and nephritis phenotype was observed for 6 months. Compared with vector-MSCs treated mice, the hOXR1-MSCs administrated mice showed significantly decreased blood urea nitrogen (BUN), proteinuria and ameliorated renal pathology. hOXR1-MSCs transplantation significantly reduced macrophage and T lymphocyte infiltration by inhibiting the expression of CCL2, CCL7, IL-1β, IL-6 and NFκB. hOXR1-MSCs prevented hydrogen peroxide induced oxidative stress and its implantation reduced NO in mouse serum and urine and increased catalase and GPX1 to inhibit tubular cell apoptosis. In conclusion, OXR1 exerted protective effect on nephritis by suppressing inflammation and oxidative stress.