Elsevier

Journal of Proteomics

Volume 85, 24 June 2013, Pages 109-128
Journal of Proteomics

Original article
Comparative proteome analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and organ donors

https://doi.org/10.1016/j.jprot.2013.04.033Get rights and content
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open access

Highlights

  • First report on a proteome profiling of lung tissue from patients with IPF and NSIP

  • The distinct entities IPF and NSIP are proteomically similar.

  • Epithelial ER- and oxidative stress are key in the pathogenesis of both IPF and NSIP.

  • Only few, but important differences exist between IPF and NSIP at the proteomic level.

  • Enhanced protection mechanisms against oxidative-/ER stress distinguish NSIP from IPF.

Abstract

Among the idiopathic interstitial pneumonias (IIP), the two entities IPF and NSIP seem to be clinically related, but NSIP has a better outcome. The proteomic signatures which distinguish NSIP from IPF remain still elusive. We therefore performed comparative proteomic analysis of peripheral lung tissue from patients with sporadic IPF (n = 14) and fibrotic NSIP (fNSIP, n = 8) and organ donors (Controls, n = 10), by using the 2-dimensional DIGE technique and MALDI-TOF-MS. The study revealed that the proteomic profiles of IPF and fNSIP were quite similar. Among the upregulated proteins in IPF and fNSIP were stress-induced genes involved in the ER stress-pathway, whereas downregulated proteins in IPF and fNSIP included antiapoptotic factors and antifibrotic molecules. The comparison fNSIP versus IPF indicated upregulation of subunits of the proteasome activator complex and antioxidant enzymes of the peroxiredoxin family. We conclude, that only few protein expression changes exist between IPF and fNSIP, and that epithelial ER- and oxidative stress play a major role in the pathogenesis of both diseases. In contrast to IPF, intracellular clearance of ROS and misfolded protein carbonyls seem to be enhanced in fNSIP due to enhanced expression of antioxidant acting proteins, and may explain the better outcome and survival in patients with fNSIP.

Biological significance

IPF and fibrotic NSIP (fNSIP) belong to the idiopathic interstitial pneumonias and are usually fatal, but fNSIP has a better outcome. In order to identify molecular mechanisms and differences between IPF and fNSIP, we herein present results of a comparative proteome analysis of IPF, fNSIP and control lung tissue. Our data including validation experiments suggest that ER stress and a general stress-response as well as the decline of antioxidant capacity in alveolar epithelium is key in the pathogenesis of IPF and fNSIP. In addition, we could observe a signature of an increased alveolar epithelial protection against oxidative and ER-stress in fNSIP as compared to IPF, which could help to explain the better outcome of fNSIP patients.

Keywords

Idiopathic pulmonary fibrosis (IPF)
Non-specific interstitial pneumonia (NSIP)
DIGE technique
Type-II alveolar epithelial cell (AECII)
Oxidative stress
Antioxidant

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