Genes related to emphysema are enriched for ubiquitination pathways

BMC Pulmonary Medicine

Ma’en Obeidat²  Peter D Paré²  Melody Morris³  Michael Crackower³  Gary O’Neill³  Don D Sin²  James C Hogg²  Christopher J Roberts³  Silvija Coulter³  Leanna Loy²  Jerry Wong²  Honglin Luo²  Shizu Hayashi²  Mark Elliott²  Brian Kennedy³  James Mortimer³  Yves Boie³  I-Ming Wang³  Sergey Stepaniants¹ 

[1] Covance Genomics Laboratory, Indianapolis, USA;University of British Columbia Centre for Heart and Lung Innovation, St Paul’s Hospital, 1081 Burrard St, Vancouver V6Z 1Y6, BC, Canada;Merck Research Laboratory, Rahway, USA

关键词: Protein ubquitination;    Cigarette smoking;    mRNA;    Transcriptional analysis;    Gene expression;    Surface area to lung volume ratio;    Pulmonary emphysema;   

Others  :  1091163
DOI  :  10.1186/1471-2466-14-187

 received in 2014-04-05, accepted in 2014-11-19,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Stepaniants et al.; licensee BioMed Central Ltd.

【 图 表 】

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