Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Altered Expression of Intraflagellar Transport Genes is Associated with Short Cilia in Smoking and COPD

ABSTRACT: Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD. Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject. Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. 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. Answer to the Question 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. Gene expression was assessed for 40 intraflagellar transport related genes in the LAE of nonsmokers (n=21) and healthy smokers (n=31) and the SAE of an independent group of nonsmokers (n=28) and healthy smokers (n=69). Cilia length was assessed in a total of 228 airway epithelium samples, including 120 LAE samples and 108 SAE samples; a subset of the 228 samples is represented among the 149 samples in this Series.

ORGANISM(S): Homo sapiens

SUBMITTER: Yael Strulovici-Barel

PROVIDER: E-GEOD-43939 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

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

PloS one 20140120 1

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, w ...[more]

PMID: 24465567

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Altered Expression of Intraflagellar Transport Genes is Associated with Short Cilia in Smoking and COPD

Publications

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

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