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Intraflagellar Transport Gene Expression Associated with Short Cilia in Smoking and COPD
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 t...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896362/ https://www.ncbi.nlm.nih.gov/pubmed/24465567 http://dx.doi.org/10.1371/journal.pone.0085453 |
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author | 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 G. Tilley, Ann E. |
author_facet | 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 G. Tilley, Ann E. |
author_sort | Hessel, Justina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3896362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38963622014-01-24 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 G. Tilley, Ann E. PLoS One Research Article 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. Public Library of Science 2014-01-20 /pmc/articles/PMC3896362/ /pubmed/24465567 http://dx.doi.org/10.1371/journal.pone.0085453 Text en © 2014 Hessel et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 G. Tilley, Ann E. Intraflagellar Transport Gene Expression Associated with Short Cilia in Smoking and COPD |
title | Intraflagellar Transport Gene Expression Associated with Short Cilia in Smoking and COPD |
title_full | Intraflagellar Transport Gene Expression Associated with Short Cilia in Smoking and COPD |
title_fullStr | Intraflagellar Transport Gene Expression Associated with Short Cilia in Smoking and COPD |
title_full_unstemmed | Intraflagellar Transport Gene Expression Associated with Short Cilia in Smoking and COPD |
title_short | Intraflagellar Transport Gene Expression Associated with Short Cilia in Smoking and COPD |
title_sort | intraflagellar transport gene expression associated with short cilia in smoking and copd |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896362/ https://www.ncbi.nlm.nih.gov/pubmed/24465567 http://dx.doi.org/10.1371/journal.pone.0085453 |
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