Down-regulation of the canonical wnt β-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD

Rui Wang, Joumana Ahmed, Guoqing Wang, Ibrahim Hassan, Yael Strulovici-Barel, Neil R. Hackett, Ronald Crystal

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Background: The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process. We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state. Methodology/Principal Findings: Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD. Thirty-three of 56 known Wnt-related genes were expressed in the SAE. Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes. Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro. Conclusions/Significance: Smoking down-regulates the Wnt pathway in the human airway epithelium. In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.

Original languageEnglish
Article numbere14793
JournalPLoS One
Volume6
Issue number4
DOIs
Publication statusPublished - 20 Apr 2011
Externally publishedYes

Fingerprint

Catenins
Wnt Signaling Pathway
Chronic Obstructive Pulmonary Disease
epithelium
Down-Regulation
Epithelium
Genes
Smoking
Tissue
genes
Tobacco Products
T Cell Transcription Factor 1
bronchoscopy
smoking (habit)
cigarettes
Bronchoscopy
smoke
Microarrays
Smoke
immunohistochemistry

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Down-regulation of the canonical wnt β-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD. / Wang, Rui; Ahmed, Joumana; Wang, Guoqing; Hassan, Ibrahim; Strulovici-Barel, Yael; Hackett, Neil R.; Crystal, Ronald.

In: PLoS One, Vol. 6, No. 4, e14793, 20.04.2011.

Research output: Contribution to journalArticle

Wang, Rui ; Ahmed, Joumana ; Wang, Guoqing ; Hassan, Ibrahim ; Strulovici-Barel, Yael ; Hackett, Neil R. ; Crystal, Ronald. / Down-regulation of the canonical wnt β-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD. In: PLoS One. 2011 ; Vol. 6, No. 4.
@article{86449e2faadd4ba8b0340fdac98b7c49,
title = "Down-regulation of the canonical wnt β-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD",
abstract = "Background: The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process. We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state. Methodology/Principal Findings: Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD. Thirty-three of 56 known Wnt-related genes were expressed in the SAE. Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes. Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro. Conclusions/Significance: Smoking down-regulates the Wnt pathway in the human airway epithelium. In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.",
author = "Rui Wang and Joumana Ahmed and Guoqing Wang and Ibrahim Hassan and Yael Strulovici-Barel and Hackett, {Neil R.} and Ronald Crystal",
year = "2011",
month = "4",
day = "20",
doi = "10.1371/journal.pone.0014793",
language = "English",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Down-regulation of the canonical wnt β-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD

AU - Wang, Rui

AU - Ahmed, Joumana

AU - Wang, Guoqing

AU - Hassan, Ibrahim

AU - Strulovici-Barel, Yael

AU - Hackett, Neil R.

AU - Crystal, Ronald

PY - 2011/4/20

Y1 - 2011/4/20

N2 - Background: The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process. We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state. Methodology/Principal Findings: Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD. Thirty-three of 56 known Wnt-related genes were expressed in the SAE. Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes. Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro. Conclusions/Significance: Smoking down-regulates the Wnt pathway in the human airway epithelium. In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.

AB - Background: The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process. We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state. Methodology/Principal Findings: Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD. Thirty-three of 56 known Wnt-related genes were expressed in the SAE. Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes. Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro. Conclusions/Significance: Smoking down-regulates the Wnt pathway in the human airway epithelium. In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.

UR - http://www.scopus.com/inward/record.url?scp=79954527594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954527594&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0014793

DO - 10.1371/journal.pone.0014793

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e14793

ER -