EGF-Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis of Smoking-Induced Lesions in the Human Airway Epithelium

Wu Lin Zuo, Jing Yang, Kazunori Gomi, Ion Wa Chao, Ronald Crystal, Renat Shaykhiev

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The airway epithelium of cigarette smokers undergoes dramatic remodeling with hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia, altered ciliated cell differentiation and decreased junctional barrier integrity, relevant to chronic obstructive pulmonary disease and lung cancer. In this study, we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) is induced by smoking in human airway epithelium as a result of epidermal growth factor (EGF)-driven squamous differentiation of airway BC stem/progenitor cells. In turn, AREG induced a unique EGFR activation pattern in human airway BC, distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered ciliated cell differentiation and impaired barrier integrity. Further, AREG promoted its own expression and suppressed expression of EGF, establishing an autonomous self-amplifying signaling loop in airway BC relevant for promotion of EGF-independent hyperplastic phenotypes. Thus, EGF-AREG interplay in airway BC stem/progenitor cells is one of the mechanisms that mediates the interconnected pathogenesis of all major smoking-induced lesions in the human airway epithelium. Stem Cells 2017;35:824–837.

Original languageEnglish
Pages (from-to)824-837
Number of pages14
JournalStem Cells
Volume35
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Stem Cells
Epithelium
Smoking
Epidermal Growth Factor Receptor
Hyperplasia
Cell Differentiation
Lung Neoplasms
Metaplasia
Mucus
Tobacco Products
Chronic Obstructive Pulmonary Disease
Epithelial Cells
Amphiregulin
Ligands
Phenotype

Keywords

  • Airway basal cells
  • Chronic obstructive pulmonary disease
  • Epidermal growth factor receptor
  • Hyperplasia
  • Metaplasia

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

EGF-Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis of Smoking-Induced Lesions in the Human Airway Epithelium. / Zuo, Wu Lin; Yang, Jing; Gomi, Kazunori; Chao, Ion Wa; Crystal, Ronald; Shaykhiev, Renat.

In: Stem Cells, Vol. 35, No. 3, 01.03.2017, p. 824-837.

Research output: Contribution to journalArticle

Zuo, Wu Lin ; Yang, Jing ; Gomi, Kazunori ; Chao, Ion Wa ; Crystal, Ronald ; Shaykhiev, Renat. / EGF-Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis of Smoking-Induced Lesions in the Human Airway Epithelium. In: Stem Cells. 2017 ; Vol. 35, No. 3. pp. 824-837.
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