title: Comparative transcriptional profiling of 3 murine models of SLE nephritis reveals both unique and shared regulatory networks.
abstract: OBJECTIVE
  To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease.
  
  
  METHODS
  Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR.
  
  
  RESULTS
  955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss.
  
  
  CONCLUSIONS
  These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune-mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis.
authors.affiliation: Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, New York, New York, United States of America.
authors.forename: Ramalingam
authors.initials: R
authors.lastname: Bethunaickan
authors.forename: Celine C
authors.initials: CC
authors.lastname: Berthier
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Anne
authors.initials: A
authors.lastname: Davidson
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050199:Podocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology