title: Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.
abstract: BACKGROUND
  Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology.
  
  
  METHODS
  Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry.
  
  
  RESULTS
  Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) < 0.05] were chosen for cluster analysis. From the expression profile, acute inflammatory reactions characterized by the elevation of various cytokines, including interleukin (IL)-1 and IL-6, were identified within 3 days of disease onset. After 7 days, tissue remodeling response was prominent with highly induced extracellular-matrix (ECM) genes. Although cytokines related to lymphocyte activation were not detected, monocyte or mesangial cell proliferation-related genes were increased. Tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) pathway were consistently activated along the entire disease progression, inducing various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1.
  
  
  CONCLUSIONS
  We made a large-scale gene expression time table for mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.
authors.affiliation: Seoul National University Biomedical Informatics (SNUBI), Seoul, Korea.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Il Soo
authors.initials: IS
authors.lastname: Ha
authors.forename: Chang-Il
authors.initials: CI
authors.lastname: Hwang
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Yang
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.forename: Yun Anna
authors.initials: YA
authors.lastname: Cao
authors.forename: Sangdun
authors.initials: S
authors.lastname: Choi
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009395:Nephritis, Interstitial / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011817:Rabbits
chemical_list: D000936:Antigen-Antibody Complex; D016207:Cytokines; D016328:NF-kappa B