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Genes related to emphysema are enriched for ubiquitination pathways Stepaniants, Sergey; Wang, I-Ming; Boie, Yves; Mortimer, James; Kennedy, Brian; Elliott, Mark; Hayashi, Shizu; Luo, Honglin; Wong, Jerry; Loy, Leanna; Coulter, Silvija; Roberts, Christopher J.; Hogg, James C.; Sin, Don D.; O’Neill, Gary; Crackower, Michael; Morris, Melody; Paré, Peter D.; Obeidat, Ma’en

Abstract

Background: Increased small airway resistance and decreased lung elasticity contribute to the airflow limitation in chronic obstructive pulmonary disease (COPD). The lesion that corresponds to loss of lung elasticity is emphysema; the small airway obstruction is due to inflammatory narrowing and obliteration. Despite their convergence in altered physiology, different mechanisms contribute to these processes. The relationships between gene expression and these specific phenotypes may be more revealing than comparison with lung function. Methods We measured the ratio of alveolar surface area to lung volume (SA/V) in lung tissue from 43 smokers. Two samples from 21 subjects, in which SA/V differed by >49 cm2/mL were profiled to select genes whose expression correlated with SA/V. Significant genes were tested for replication in the 22 remaining subjects. Results The level of expression of 181 transcripts was related to SA/V ( p < 0.05). When these genes were tested in the 22 remaining subjects as a replication, thirty of the 181 genes remained significantly associated with SA/V (P < 0.05) and the direction of association was the same in 164/181. Pathway and network analysis revealed enrichment of genes involved in protein ubiquitination, and western blotting showed altered expression of genes involved in protein ubiquitination in obstructed individuals. Conclusion This study implicates modified protein ubiquitination and degradation as a potentially important pathway in the pathogenesis of emphysema.

Item Metadata

Title
Genes related to emphysema are enriched for ubiquitination pathways
Creator
Stepaniants, Sergey; Wang, I-Ming; Boie, Yves; Mortimer, James; Kennedy, Brian; Elliott, Mark; Hayashi, Shizu; Luo, Honglin; Wong, Jerry; Loy, Leanna; Coulter, Silvija; Roberts, Christopher J.; Hogg, James C.; Sin, Don D.; O’Neill, Gary; Crackower, Michael; Morris, Melody; Paré, Peter D.; Obeidat, Ma’en
Publisher
BioMed Central
Date Issued
2014-11-29
Description
Background: Increased small airway resistance and decreased lung elasticity contribute to the airflow limitation in chronic obstructive pulmonary disease (COPD). The lesion that corresponds to loss of lung elasticity is emphysema; the small airway obstruction is due to inflammatory narrowing and obliteration. Despite their convergence in altered physiology, different mechanisms contribute to these processes. The relationships between gene expression and these specific phenotypes may be more revealing than comparison with lung function. Methods We measured the ratio of alveolar surface area to lung volume (SA/V) in lung tissue from 43 smokers. Two samples from 21 subjects, in which SA/V differed by >49 cm2/mL were profiled to select genes whose expression correlated with SA/V. Significant genes were tested for replication in the 22 remaining subjects. Results The level of expression of 181 transcripts was related to SA/V ( p < 0.05). When these genes were tested in the 22 remaining subjects as a replication, thirty of the 181 genes remained significantly associated with SA/V (P < 0.05) and the direction of association was the same in 164/181. Pathway and network analysis revealed enrichment of genes involved in protein ubiquitination, and western blotting showed altered expression of genes involved in protein ubiquitination in obstructed individuals. Conclusion This study implicates modified protein ubiquitination and degradation as a potentially important pathway in the pathogenesis of emphysema.
Genre
Article
Type
Text
Language
eng
Date Available
2015-12-22
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0221552
URI
http://hdl.handle.net/2429/56019
Affiliation
Other UBC; Non UBC
Citation
BMC Pulmonary Medicine. 2014 Nov 29;14(1):187
Publisher DOI
10.1186/1471-2466-14-187
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Stepaniants et al.; licensee BioMed Central Ltd.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)