Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease. Academic Article uri icon

Overview

MeSH

  • Aged
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Humans
  • Immediate-Early Proteins
  • Lung
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Smoking
  • Transcription Factors

MeSH Major

  • Gene Expression Profiling
  • Gene Expression Regulation
  • Pulmonary Disease, Chronic Obstructive

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.

publication date

  • October 12, 2004

has subject area

  • Aged
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Immediate-Early Proteins
  • Lung
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Pulmonary Disease, Chronic Obstructive
  • Smoking
  • Transcription Factors

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC522001

Digital Object Identifier (DOI)

  • 10.1073/pnas.0401168101

PubMed ID

  • 15469929

Additional Document Info

start page

  • 14895

end page

  • 14900

volume

  • 101

number

  • 41