Increased expression of transforming growth factor-β1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD)

H. Takizawa, M. Tanaka, K. Takami, T. Ohtoshi, K. Ito, M. Satoh, Y. Okada, F. Yamasawa, K. Nakahara, A. Umeda

Research output: Contribution to journalArticlepeer-review

312 Citations (Scopus)

Abstract

Tobacco smoke is believed to cause small airway disease and then chronic obstructive pulmonary disease (COPD), but the molecular mechanisms by which small airway obstruction occurs remain unknown. To study the gene expression levels of transforming growth factor (TGF)-β1, a potent fibrogenic factor, in small airway epithelium from smokers and patients with COPD, we harvested highly pure samples of epithelial cells from small airways under direct vision by using an ultrathin bronchofiberscope BF-2.7T (outer diameter 2.7 mm with a biopsy channel of 0.8 mm in diameter). The expression levels of TGF-β1 were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA levels of TGF-β1 corrected by β-actin transcripts were significantly higher in the smoking group and patients with COPD than those in nonsmokers (p < 0.01). Furthermore, among smokers and patients with COPD, TGF-β1 mRNA levels correlated positively with the extent of smoking history (pack-years) and the degree of small airway obstruction as assessed by measurements of flow-volume curves. Immunocytochemistry of the cells demonstrated more intense stainings for TGF-β1 in samples from smokers and patients with COPD than from nonsmokers. Spontaneously released immunoreactive TGF-β1 levels from cultured epithelial cells were more elevated in subjects with a history of smoking and patients with COPD than in nonsmokers. Our study showed a close link between smoking and expression of TGF-β1 in small airways. Our results also suggested that small airway epithelial cells might be involved in obstructive changes found in smokers and patients with COPD.

Original languageEnglish
Pages (from-to)1476-1483
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume163
Issue number6
DOIs
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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