Expression of Smad7 in bronchial epithelial cells is inversely correlated to basement membrane thickness and airway hyperresponsiveness in patients with asthma

J Allergy Clin Immunol. 2002 Dec;110(6):873-8. doi: 10.1067/mai.2002.129236.


Background: Smad7 is an intracellular antagonist of transforming growth factor beta (TGF-beta) signaling, which could determine the intensity or duration of the TGF-beta signal. Because TGF-beta has been implicated in the development of airway remodeling in asthma on the basis of its strong capacity to induce extracellular matrix production, it is possible that Smad7 also plays some roles in the regulation of the process.

Objective: We sought to determine the relationships between Smad7 expression in bronchial biopsy samples from asthmatic subjects and clinicopathologic features.

Methods: Bronchial biopsy specimens were obtained from 40 asthmatic subjects and 6 healthy control subjects. Expression levels of Smad7 on a histologic section were estimated by immunohistochemical staining. In addition, the roles of Smad7 in TGF-beta-mediated transcriptional responses were studied by in vitro studies.

Results: Smad7 immunoreactivity was detected mainly in bronchial epithelial cells in control and asthmatic subjects. Interestingly, asthmatic subjects exhibited less Smad7 immunoreactivity in bronchial epithelial cells than normal subjects. Expression levels of Smad7 in bronchial epithelial cells were inversely correlated with basement membrane thickness and airway hyperresponsiveness in asthmatic subjects. In addition, abrogation of endogenous Smad7 expression through use of an antisense oligonucleotide enhanced transcriptional responses to TGF-beta, whereas overexpression of Smad7 inhibited TGF-beta-induced plasminogen activator inhibitor 1production in a human bronchial epithelial cell line, BEAS2B cells.

Conclusion: These findings suggest that Smad7 is a key molecule that defines the susceptibility of bronchial epithelial cells to TGF-beta action and that regulation of Smad7 expression in bronchial epithelial cells might be related to the development of airway remodeling and airway hyperresponsiveness in asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma / metabolism
  • Asthma / pathology*
  • Basement Membrane / pathology
  • Bronchi / chemistry*
  • Bronchi / pathology
  • Bronchial Hyperreactivity / metabolism*
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / physiology
  • Epithelial Cells / chemistry
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Plasminogen Activator Inhibitor 1 / genetics
  • Smad7 Protein
  • Trans-Activators / analysis*
  • Trans-Activators / physiology
  • Transcription, Genetic
  • Transforming Growth Factor beta / physiology


  • DNA-Binding Proteins
  • Plasminogen Activator Inhibitor 1
  • SMAD7 protein, human
  • Smad7 Protein
  • Trans-Activators
  • Transforming Growth Factor beta