Modification of gene expression of the small airway epithelium in response to cigarette smoking. Academic Article uri icon

Overview

MeSH

  • Bronchoscopy
  • Gene Expression Profiling
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction

MeSH Major

  • Biomarkers
  • Gene Expression Regulation
  • Respiratory Mucosa
  • Smoking

abstract

  • The earliest morphologic evidence of changes in the airways associated with chronic cigarette smoking is in the small airways. To help understand how smoking modifies small airway structure and function, we developed a strategy using fiberoptic bronchoscopy and brushing to sample the human small airway (10th-12th order) bronchial epithelium to assess gene expression (Affymetrix HG-U133A and HG-133 Plus 2.0 array) in phenotypically normal smokers (n = 16, 25 +/- 7 pack-years) compared to matched nonsmokers (n = 17). Compared to samples from large (second to third order) bronchi, the small airway samples had a higher proportion of ciliated cells, but less basal, undifferentiated, and secretory cells, and contained Clara cells. Even though the smokers were phenotypically normal, microarray analysis of gene expression of the small airway epithelium of the smokers compared to the nonsmokers demonstrated up- and downregulation of genes in multiple categories relevant to the pathogenesis of chronic obstructive lung disease (COPD), including genes coding for cytokines/innate immunity, apoptosis, mucin, response to oxidants and xenobiotics, and general cellular processes. In the context that COPD starts in the small airways, these gene expression changes in the small airway epithelium in phenotypically normal smokers are candidates for the development of therapeutic strategies to prevent the onset of COPD.

publication date

  • January 2007

has subject area

  • Biomarkers
  • Bronchoscopy
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive
  • RNA, Messenger
  • Respiratory Mucosa
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1007/s00109-006-0103-z

PubMed ID

  • 17115125

Additional Document Info

start page

  • 39

end page

  • 53

volume

  • 85

number

  • 1