FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro. Academic Article uri icon

Overview

MeSH

  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Transcription, Genetic

MeSH Major

  • Cilia
  • Forkhead Transcription Factors
  • Respiratory Mucosa
  • Smoking

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.

publication date

  • November 2014

has subject area

  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cilia
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Humans
  • Respiratory Mucosa
  • Smoking
  • Transcription, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4224080

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2013-0363OC

PubMed ID

  • 24828273

Additional Document Info

start page

  • 688

end page

  • 700

volume

  • 51

number

  • 5