title: 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.
abstract: 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. However 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 ofOXR1on glomerulonephritis. HumanOXR1gene was integrated into genome of MSCs via lentiviral vector, and established hOXR1-MSC cell line which still maintains the differentiation property.129/svjmice with anti-glomerular basement membrane (GBM) challenge and spontaneous lupus miceB6.Sle1.Sle2.Sle3were 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. 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.
  
  
  CONCLUSIONS
  OXR1-MSCs transplantation may exert a certain protective effect on nephritis by suppressing inflammation and oxidative stress.
authors.affiliation: Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100029, China ; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Genetics, Wenzhou Medical University School of Laboratory Medicine & Life Science, Wenzhou, 325035, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Genetics, Wenzhou Medical University School of Laboratory Medicine & Life Science, Wenzhou, 325035, China.
authors.forename: Chu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Indu
authors.initials: I
authors.lastname: Raman
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.affiliation: Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100029, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
authors.affiliation: Renal Path Diagnostics, Pathologist BioMedical Laboratories, Lewisville, TX, 75067, USA.
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
authors.affiliation: Key Laboratory of Medical Genetics, Wenzhou Medical University School of Laboratory Medicine & Life Science, Wenzhou, 325035, China ; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Quan-Zhen
authors.initials: QZ
authors.lastname: Li
keywords: Oxidation resistance 1; apoptosis; inflammation; lupus nephritis; mesenchymal stem cell; oxidative stress