EGF shifts human airway basal cell fate towarda smoking-Associated airway epithelial phenotype

Renat Shaykhiev, Wu Lin Zuo, Ion Wa Chao, Tomoya Fukui, Bradley Witover, Angelika Brekman, Ronald Crystal

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The airway epitheliumof smokers acquires pathological phenotypes, including basal cell (BC) and/or goblet cell hyperplasia, squamous metaplasia, structural and functional abnormalities of ciliated cells, decreased number of secretoglobin (SCGB1A1)-expressing secretory cells, and a disordered junctional barrier. In this study, we hypothesized that smoking alters airway epithelial structure through modification of BC function via an EGF receptor (EGFR)-mediated mechanism. Analysis of the airway epithelium revealed that EGFR is enriched in airway BCs,whereas its ligand EGF is induced by smoking in ciliated cells. Exposure of BCs to EGF shifted the BC differentiation program toward the squamous and epithelial-mesenchymal transition- like phenotypes with down-regulation of genes related to ciliogenesis, secretory differentiation, and markedly reduced junctional barrier integrity, mimicking the abnormalities present in the airways of smokers in vivo. These data suggest that activation of EGFR in airway BCs by smoking-induced EGF represents a unique mechanism whereby smoking can alter airway epithelial differentiation and barrier function.

Original languageEnglish
Pages (from-to)12102-12107
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number29
DOIs
Publication statusPublished - 16 Jul 2013
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Smoking
Epidermal Growth Factor Receptor
Phenotype
Secretoglobins
Goblet Cells
Epithelial-Mesenchymal Transition
Metaplasia
Hyperplasia
Cell Differentiation
Down-Regulation
Epithelium
Cell Count
Ligands
Genes

Keywords

  • Airway Epithelial Barrier
  • Cigarette Smoking
  • Progenitor Cell

ASJC Scopus subject areas

  • General

Cite this

EGF shifts human airway basal cell fate towarda smoking-Associated airway epithelial phenotype. / Shaykhiev, Renat; Zuo, Wu Lin; Chao, Ion Wa; Fukui, Tomoya; Witover, Bradley; Brekman, Angelika; Crystal, Ronald.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 29, 16.07.2013, p. 12102-12107.

Research output: Contribution to journalArticle

Shaykhiev, Renat ; Zuo, Wu Lin ; Chao, Ion Wa ; Fukui, Tomoya ; Witover, Bradley ; Brekman, Angelika ; Crystal, Ronald. / EGF shifts human airway basal cell fate towarda smoking-Associated airway epithelial phenotype. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 29. pp. 12102-12107.
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