title: Genes related to emphysema are enriched for ubiquitination pathways.
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.
  
  
  CONCLUSIONS
  This study implicates modified protein ubiquitination and degradation as a potentially important pathway in the pathogenesis of emphysema.
authors.forename: Sergey
authors.initials: S
authors.lastname: Stepaniants
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Wang
authors.forename: Yves
authors.initials: Y
authors.lastname: Boie
authors.forename: James
authors.initials: J
authors.lastname: Mortimer
authors.forename: Brian
authors.initials: B
authors.lastname: Kennedy
authors.forename: Mark
authors.initials: M
authors.lastname: Elliott
authors.forename: Shizu
authors.initials: S
authors.lastname: Hayashi
authors.forename: Honglin
authors.initials: H
authors.lastname: Luo
authors.forename: Jerry
authors.initials: J
authors.lastname: Wong
authors.forename: Leanna
authors.initials: L
authors.lastname: Loy
authors.forename: Silvija
authors.initials: S
authors.lastname: Coulter
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Roberts
authors.forename: James C
authors.initials: JC
authors.lastname: Hogg
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.forename: Gary
authors.initials: G
authors.lastname: O'Neill
authors.forename: Michael
authors.initials: M
authors.lastname: Crackower
authors.forename: Melody
authors.initials: M
authors.lastname: Morris
authors.affiliation: University of British Columbia Centre for Heart and Lung Innovation, St Paul's Hospital, 1081 Burrard St, Vancouver V6Z 1Y6, BC, Canada. Peter.pare@hli.ubc.ca.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.forename: Ma'en
authors.initials: M
authors.lastname: Obeidat
mesh_terms: D000368:Aged; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D044783:F-Box Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000473:pathology*; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics; D011650:Pulmonary Alveoli / Q000473:pathology*; D011656:Pulmonary Emphysema / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking / Q000503:physiopathology; D025801:Ubiquitin / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D044783:F-Box Proteins; C519795:FBXL3 protein, human; C000601042:FBXO30 protein, human; C119753:RNF6 protein, human; C479419:UBB protein, human; D025801:Ubiquitin; C000601043:USP38 protein, human; D064570:Ubiquitin-Specific Proteases