Proteomic analysis of nasal epithelial cells from cystic fibrosis patients

PLoS One. 2014 Sep 30;9(9):e108671. doi: 10.1371/journal.pone.0108671. eCollection 2014.

Abstract

The pathophysiology of cystic fibrosis (CF) lung disease remains incompletely understood. New explanations for the pathogenesis of CF lung disease may be discovered by studying the patterns of protein expression in cultured human nasal epithelial cells (HNEC). To that aim, we compared the level of protein expressions in primary cultures of HNEC from nasal polyps secondary to CF (CFNP, n = 4), primary nasal polyps (NP, n = 8) and control mucosa (CTRL, n = 4) using isobaric tag for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography (LC)-MS-MS. The analysis of the data revealed 42 deregulated protein expressions in CFNP compared to NP and CTRL, suggesting that these alterations are related to CF. Overall, AmiGo analysis highlighted six major pathways important for cell functions that seem to be impaired: metabolism, G protein process, inflammation and oxidative stress response, protein folding, proteolysis and structural proteins. Among them, glucose and fatty acid metabolic pathways could be impaired in CF with nine deregulated proteins. Our proteomic study provides a reproducible set of differentially expressed proteins in airway epithelial cells from CF patients and reveals many novel deregulated proteins that could lead to further studies aiming to clarify the involvement of such proteins in CF pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chromatography, Liquid
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Fatty Acids / metabolism
  • Female
  • Gene Expression
  • Glucose / metabolism
  • Humans
  • Male
  • Metabolic Networks and Pathways
  • Mutation
  • Nasal Polyps / metabolism*
  • Nasal Polyps / pathology
  • Oxidative Stress
  • Primary Cell Culture
  • Protein Folding
  • Proteolysis
  • Proteome / analysis*
  • Proteome / genetics
  • Proteome / metabolism
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / pathology
  • Tandem Mass Spectrometry

Substances

  • CFTR protein, human
  • Fatty Acids
  • Proteome
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Glucose

Grants and funding

Funding was provided by Agence Nationale pour la Recherche -05-MRAR-02201; European Community: Life Sciences and Health Grant (LSHG-CT-2005-512044) NEUPROCF; French Foundation for Cystic Fibrosis: “Vaincre la Mucoviscidose”; Legs Poix from Chancellerie des Universités. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.