title: Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by irreversible airflow limitation. Cigarette smoking represents the main risk factor, but the specific mechanisms of COPD are not completely understood. Our aim was to identify COPD-specific proteomic changes involved in disease onset and severity. A comparative proteomic analysis of 51 lung tissues from nonsmokers, smokers, smokers with mild to moderate (stage I-II) COPD, severe to very severe COPD (stage III-IV), and patients with α-1-antitrypsin deficiency (AATD) and idiopathic pulmonary fibrosis (IPF) was performed by cysteine-specific two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Selected COPD-specific changes were validated by immunoblotting and further by ELISA in 120 induced sputum and plasma samples from nonsmokers, smokers, and patients with COPD (stage I-III). Altogether 82 altered proteins were identified comprising COPD-, AATD-, and IPF-specific, overlapping, and unspecific changes. Cathepsin D (CTSD), dihydropyrimidinase-related protein 2 (DPYSL2), transglutaminase 2 (TGM2), and tripeptidyl-peptidase 1 (TPP1) were validated as COPD-specific. TGM2 was not associated with smoking and correlated with COPD severity in lung tissue. TGM2 levels in sputum and plasma were elevated in patients with COPD (stage II-III) and correlated with lung function. In conclusion, new proteins related to COPD onset and severity could be identified with TGM2 being a novel potential diagnostic and therapeutic target for COPD. Further studies in carefully characterized cohorts are required to validate the identified changes.
authors.affiliation: Proteomics Core Facility, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu;
authors.forename: Steffen
authors.initials: S
authors.lastname: Ohlmeier
authors.affiliation: Medical Informatics and Statistics Group, University of Oulu, Oulu;
authors.forename: Pentti
authors.initials: P
authors.lastname: Nieminen
authors.affiliation: Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki;
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki;
authors.forename: Tinja
authors.initials: T
authors.lastname: Kanerva
authors.affiliation: HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki; and.
authors.forename: Mikko
authors.initials: M
authors.lastname: Rönty
authors.affiliation: Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Toljamo
authors.affiliation: Proteomics Core Facility, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu;
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bergmann
authors.affiliation: Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki;
authors.forename: Witold
authors.initials: W
authors.lastname: Mazur
authors.affiliation: Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki; ville.pulkkinen@helsinki.fi.
authors.forename: Ville
authors.initials: V
authors.lastname: Pulkkinen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000097:blood*; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects / Q000097:blood; D011503:Transglutaminases / Q000097:blood*; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D020543:Proteome; C000717608:TGM2 protein, human; D000091346:Tripeptidyl-Peptidase 1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; C000717267:TPP1 protein, human; D019204:GTP-Binding Proteins
keywords: chronic obstructive pulmonary disease (COPD); difference gel electrophoresis (DIGE); idiopathic pulmonary fibrosis (IPF); lung tissue; two-dimensional gel electrophoresis (2-DE); α-1-antitrypsin deficiency (AATD)