title: Comparative proteomic analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and lung transplant donor lungs.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which no effective therapy exists to date. To identify the molecular mechanisms underlying IPF, we performed comparative proteome analysis of lung tissue from patients with sporadic IPF (n = 14) and human donor lungs (controls, n = 10) using two-dimensional gel electrophoresis and MALDI-TOF-MS. Eighty-nine differentially expressed proteins were identified, from which 51 were up-regulated and 38 down-regulated in IPF. Increased expression of markers for the unfolded protein response (UPR), heat-shock proteins, and DNA damage stress markers indicated a chronic cell stress-response in IPF lungs. By means of immunohistochemistry, induction of UPR markers was encountered in type-II alveolar epithelial cells of IPF but not of control lungs. In contrast, up-regulation of heat-shock protein 27 (Hsp27) was exclusively observed in proliferating bronchiolar basal cells and associated with aberrant re-epithelialization at the bronchiolo-alveolar junctions. Among the down-regulated proteins in IPF were antioxidants, members of the annexin family, and structural epithelial proteins. In summary, our results indicate that IPF is characterized by epithelial cell injury, apoptosis, and aberrant epithelial proliferation.
authors.affiliation: University of Giessen Lung Center, Department of Internal Medicine II, Klinikstrasse 36, Justus-Liebig-University Giessen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Korfei
authors.forename: Sigrid
authors.initials: S
authors.lastname: Schmitt
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.forename: Ingrid
authors.initials: I
authors.lastname: Henneke
authors.forename: Philipp
authors.initials: P
authors.lastname: Markart
authors.forename: Benjamin
authors.initials: B
authors.lastname: Loeh
authors.forename: Poornima
authors.initials: P
authors.lastname: Mahavadi
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wygrecka
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Ludger
authors.initials: L
authors.lastname: Fink
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonniaud
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Günter
authors.initials: G
authors.lastname: Lochnit
authors.forename: Liliana
authors.initials: L
authors.lastname: Schaefer
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Andreas
authors.initials: A
authors.lastname: Guenther
mesh_terms: D004249:DNA Damage / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019737:Transplants; D056811:Unfolded Protein Response / Q000235:genetics
chemical_list: D005819:Genetic Markers; D006360:Heat-Shock Proteins; D011506:Proteins