FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro

Angelika Brekman, Matthew S. Walters, Ann E. Tilley, Ronald Crystal

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Airway epithelium ciliated cells play a central role in clearing the lung of inhaled pathogens and xenobiotics, and cilia length and coordinated beating are important for airway clearance. Based on in vivo studies showing that the airway epithelium of healthy smokers has shorter cilia than that of healthy nonsmokers, we investigated the mechanisms involved in cigarette smoke-mediated inhibition of ciliogenesis by assessing normal human airway basal cell differentiation in air-liquid interface (ALI) cultures in the presence of nontoxic concentrations of cigarette smoke extract (CSE). Measurements of cilia length from Day 28 ALI cultures demonstrated that CSE exposure was associated with shorter cilia (P < 0.05), reproducing the effect of cigarette smoking on cilia length observed in vivo. This phenotype correlated with a broad CSE-mediated suppression of genes involved in cilia-related transcriptional regulation, intraflagellar transport, cilia motility, structural integrity, and basal body development but not of control genes or epithelial barrier integrity. The CSE-mediated inhibition of cilia growth could be prevented by lentivirus-mediated overexpression of FOXJ1, the major cilia-related transcription factor, which led to partial reversal of expression of cilia-related genes suppressed by CSE. Together, the data suggest that components of cigarette smoke are responsible for a broad suppression of genes involved in cilia growth, but, by stimulating ciliogenesis with the transcription factor FOXJ1, it may be possible to maintain close to normal cilia length despite the stress of cigarette smoking.

Original languageEnglish
Pages (from-to)688-700
Number of pages13
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume51
Issue number5
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Fingerprint

Cilia
Smoke
Tobacco Products
Epithelium
Growth
Genes
Bridge clearances
Transcription Factors
Inhibition (Psychology)
In Vitro Techniques
Smoking
Air
Liquids
Structural integrity
Pathogens
Xenobiotics
Basal Bodies
Cell culture
Lentivirus
Cells

Keywords

  • Cigarette smoke
  • Ciliogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro. / Brekman, Angelika; Walters, Matthew S.; Tilley, Ann E.; Crystal, Ronald.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 51, No. 5, 01.01.2014, p. 688-700.

Research output: Contribution to journalArticle

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