Abstract

Doc number: 187

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.

Details

Title
Genes related to emphysema are enriched for ubiquitination pathways
Author
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
Publication year
2014
Publication date
2014
Publisher
BioMed Central
e-ISSN
14712466
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1635638288
Copyright
© 2014 Stepaniants et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.