Gene Set: NING_CHRONIC_OBSTRUCTIVE_PULMONARY_DISEASE_DN

Standard name NING_CHRONIC_OBSTRUCTIVE_PULMONARY_DISEASE_DN
Systematic name M14027
Brief description Down-regulated genes in lung tissue of smokers with chronic obstructive pulmonary disease (COPD) vs smokers without disease (GOLD-2 vs GOLD-0).
Full description or abstract To better understand the molecular basis of chronic obstructive pulmonary disease (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis to compare the gene expression patterns of lung tissues from COPD and control smokers. A total of 59,343 tags corresponding to 26,502 transcripts were sequenced in SAGE analyses. A total of 327 genes were differentially expressed (1.5-fold up- or down-regulated). Microarray analysis using the same RNA source detected 261 transcripts that were differentially expressed to a significant degree between GOLD-2 and GOLD-0 smokers. We confirmed the altered expression of a select number of genes by using real-time quantitative RT-PCR. These genes encode for transcription factors (EGR1 and FOS), growth factors or related proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA), and extracellular matrix protein (COL1A1). Immunofluorescence studies on the same lung specimens localized the expression of Egr-1, CTGF, and Cyr61 to alveolar epithelial cells, airway epithelial cells, and stromal and inflammatory cells of GOLD-2 smokers. Cigarette smoke extract induced Egr-1 protein expression and increased Egr-1 DNA-binding activity in human lung fibroblast cells. Cytomix (tumor necrosis factor alpha, IL-1beta, and IFN-gamma) treatment showed that the activity of matrix metalloproteinase-2 (MMP-2) was increased in lung fibroblasts from EGR1 control (+/+) mice but not detected in that of EGR1 null (-/-) mice, whereas MMP-9 was regulated by EGR1 in a reverse manner. Our study represents the first comprehensive analysis of gene expression on GOLD-2 versus GOLD-0 smokers and reveals previously unreported candidate genes that may serve as potential molecular targets in COPD.
Collection ARCHIVED: Archived Founder gene sets that are referenced by current Hallmarks
      C2_CGP: Archived chemical and genetic perturbations
Source publication Pubmed 15469929   Authors: Ning W,Li CJ,Kaminski N,Feghali-Bostwick CA,Alber SM,Di YP,Otterbein SL,Song R,Hayashi S,Zhou Z,Pinsky DJ,Watkins SC,Pilewski JM,Sciurba FC,Peters DG,Hogg JC,Choi AM
Exact source Table 8S: Ratio G2/G0 =< -1.5
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Organism Homo sapiens
Contributed by Kate Stafford (MSigDB Team)
Source platform UniGene_ID
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Version history 3.0: Renamed from NING_COPD_DN

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