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Delivering Oxidation Resistance-1 (OXR1) to Mouse Kidney by Genetic Modified Mesenchymal Stem Cells Exhibited Enhanced Protection against Nephrotoxic Serum Induced Renal Injury and Lupus Nephritis

Yajuan Li, Wei Li, Chu Liu, Mei Yan, Indu Raman, Yong Du, Xiangdong Fang, Xin J. Zhou, Chandra Mohan and Quan-Zhen Li

Objective: To elucidate the role of oxidation resistance 1 (OXR1) gene Oxidative stress plays a pivotal role in pathogenesis of immune-mediated nephritis. Recently we identified oxidation resistance 1 (OXR1) is conventionally expressed in eukaryotes and has an ability to prevent oxidative damage caused by various oxidative stresses. Although the protective effect of OXR1 in immune-associated inflammatory response and oxidative damage is not clear and will be investigated in this study. Methods: We utilized mesenchymal stem cells (MSCs) as vehicles to carry OXR1 into the injured kidneys of nephritis model mice and investigated the influence of OXR1 on glomerulonephritis. Human OXR1 gene was integrated into genome of MSCs via lentiviral vector, and established hOXR1-MSC cell line which still maintains the differentiation property. 129/svj mice with anti-glomerular basement membrane (GBM) challenge and spontaneous lupus mice B6.Sle1.Sle2.Sle3 were injected with hOXR1-MSCs (i.v. injection) to evaluate the function of hOXR1. Immunohistochemistry was used to appraise the renal pathology and Tunel staining was applied to detect cell apoptosis. Results: Compared with control mice, hOXR1-MSCs administration showed significantly decreased blood urea nitrogen (BUN), proteinuria and ameliorated renal pathological damage. And hOXR1-MSCs transplantation significantly reduced macrophage and T lymphocyte infiltration by inhibiting the expression of CCL2, CCL7, IL-1β, IL-6 and NFκB in mouse kidney. Moreover, hOXR1-MSCs prevented hydrogen peroxide (H2O2)-induced oxidative stress and its implantation reduced nitric oxide (NO) in mouse serum and urine to inhibit tubular cell apoptosis. Conclusion: OXR1-MSCs transplantation may exert a certain protective effect on nephritis by suppressing inflammation and oxidative stress.