title: Comparative proteome analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and organ donors.
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.
  
  
  CONCLUSIONS
  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.
authors: Universities of Giessen and Marburg Lung Center-UGMLC, D-35392 Giessen, Germany.
authors: Martina
authors: M
authors: Korfei
authors: Daniel
authors: D
authors: von der Beck
authors: Ingrid
authors: I
authors: Henneke
authors: Philipp
authors: P
authors: Markart
authors: Clemens
authors: C
authors: Ruppert
authors: Poornima
authors: P
authors: Mahavadi
authors: Bahil
authors: B
authors: Ghanim
authors: Walter
authors: W
authors: Klepetko
authors: Ludger
authors: L
authors: Fink
authors: Silke
authors: S
authors: Meiners
authors: Oliver Holger
authors: OH
authors: Krämer
authors: Werner
authors: W
authors: Seeger
authors: Carlo
authors: C
authors: Vancheri
authors: Andreas
authors: A
authors: Guenther
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D054988:Idiopathic Interstitial Pneumonias / Q000378:metabolism* / Q000473:pathology; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000096:biosynthesis*; D014019:Tissue Donors
chemical_list: D020543:Proteome