Intraflagellar transport gene expression associated with short cilia in smoking and COPD

Justina Hessel, Jonna Heldrich, Jennifer Fuller, Michelle R. Staudt, Sharon Radisch, Charleen Hollmann, Ben Gary Harvey, Robert J. Kaner, Jacqueline Salit, Jenny Yee-Levin, Sriram Sridhar, Sreekumar Pillai, Holly Hilton, Gerhard Wolff, Hans Bitter, Sudha Visvanathan, Jay Fine, Christopher S. Stevenson, Ronald Crystal, Ann E. Tilley

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Smoking and COPD are associated with decreased mucociliary clearance, and healthy smokers have shorter cilia in the large airway than nonsmokers. We hypothesized that changes in cilia length are consistent throughout the airway, and we further hypothesized that smokers with COPD have shorter cilia than healthy smokers. Because intraflagellar transport (IFT) is the process by which cilia of normal length are produced and maintained, and alterations in IFT lead to short cilia in model organisms, we also hypothesized that smoking induces changes in the expression of IFT-related genes in the airway epithelium of smokers and smokers with COPD. To assess these hypotheses, airway epithelium was obtained via bronchoscopic brushing. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject and Affymetrix microarrays were used to evaluate IFT gene expression in nonsmokers and healthy smokers in 2 independent data sets from large and small airway as well as in COPD smokers in a data set from the small airway. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. The gene expression data confirmed that a set of 8 IFT genes were down-regulated in smokers in both data sets; however, no differences were seen in COPD smokers compared to healthy smokers. These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies.

Original languageEnglish
Article numbere85453
JournalPLoS One
Volume9
Issue number1
DOIs
Publication statusPublished - 20 Jan 2014
Externally publishedYes

Fingerprint

Cilia
cilia
Gene expression
Chronic Obstructive Pulmonary Disease
Smoking
Gene Expression
gene expression
Genes
Mucociliary Clearance
epithelium
Epithelium
Microarrays
genes

ASJC Scopus subject areas

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

Cite this

Hessel, J., Heldrich, J., Fuller, J., Staudt, M. R., Radisch, S., Hollmann, C., ... Tilley, A. E. (2014). Intraflagellar transport gene expression associated with short cilia in smoking and COPD. PLoS One, 9(1), [e85453]. https://doi.org/10.1371/journal.pone.0085453

Intraflagellar transport gene expression associated with short cilia in smoking and COPD. / Hessel, Justina; Heldrich, Jonna; Fuller, Jennifer; Staudt, Michelle R.; Radisch, Sharon; Hollmann, Charleen; Harvey, Ben Gary; Kaner, Robert J.; Salit, Jacqueline; Yee-Levin, Jenny; Sridhar, Sriram; Pillai, Sreekumar; Hilton, Holly; Wolff, Gerhard; Bitter, Hans; Visvanathan, Sudha; Fine, Jay; Stevenson, Christopher S.; Crystal, Ronald; Tilley, Ann E.

In: PLoS One, Vol. 9, No. 1, e85453, 20.01.2014.

Research output: Contribution to journalArticle

Hessel, J, Heldrich, J, Fuller, J, Staudt, MR, Radisch, S, Hollmann, C, Harvey, BG, Kaner, RJ, Salit, J, Yee-Levin, J, Sridhar, S, Pillai, S, Hilton, H, Wolff, G, Bitter, H, Visvanathan, S, Fine, J, Stevenson, CS, Crystal, R & Tilley, AE 2014, 'Intraflagellar transport gene expression associated with short cilia in smoking and COPD', PLoS One, vol. 9, no. 1, e85453. https://doi.org/10.1371/journal.pone.0085453
Hessel J, Heldrich J, Fuller J, Staudt MR, Radisch S, Hollmann C et al. Intraflagellar transport gene expression associated with short cilia in smoking and COPD. PLoS One. 2014 Jan 20;9(1). e85453. https://doi.org/10.1371/journal.pone.0085453
Hessel, Justina ; Heldrich, Jonna ; Fuller, Jennifer ; Staudt, Michelle R. ; Radisch, Sharon ; Hollmann, Charleen ; Harvey, Ben Gary ; Kaner, Robert J. ; Salit, Jacqueline ; Yee-Levin, Jenny ; Sridhar, Sriram ; Pillai, Sreekumar ; Hilton, Holly ; Wolff, Gerhard ; Bitter, Hans ; Visvanathan, Sudha ; Fine, Jay ; Stevenson, Christopher S. ; Crystal, Ronald ; Tilley, Ann E. / Intraflagellar transport gene expression associated with short cilia in smoking and COPD. In: PLoS One. 2014 ; Vol. 9, No. 1.
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