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- Title
Gene expression profiling of anti-GBM glomerulonephritis model: The role of NF-κB in immune complex kidney disease.
- Authors
Kim, Ju Han; Soo Ha, Il; Hwang, Chang-Il; Lee, Young-Ju; Kim, Jihoon; Yang, Seung-Hee; Kim, Yon Su; Cao, Yun Anna; Choi, Sangdun; Park, Woong-Yang
- Abstract
Gene expression profiling of anti-GBM glomerulonephritis model: The role of NF-κB in immune complex kidney disease.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-α (TNF-α) and nuclear factor-κB (NF-κB) pathway were consistently activated along the entire disease progression, inducing various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1.Conclusion.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.
- Subjects
GENE expression; GENETIC regulation; KIDNEY diseases; GLOMERULONEPHRITIS; CYTOKINES; URINARY organs
- Publication
Kidney International, 2004, Vol 66, Issue 5, p1826
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1111/j.1523-1755.2004.00956.x