PMID- 27084846
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20211204
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 310
IP  - 11
DP  - 2016 Jun 1
TI  - Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable 
      chronic obstructive pulmonary disease.
PG  - L1155-65
LID - 10.1152/ajplung.00021.2016 [doi]
AB  - 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 alpha-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.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Ohlmeier, Steffen
AU  - Ohlmeier S
AD  - Proteomics Core Facility, Biocenter Oulu, Faculty of Biochemistry and Molecular 
      Medicine, University of Oulu, Oulu;
FAU - Nieminen, Pentti
AU  - Nieminen P
AD  - Medical Informatics and Statistics Group, University of Oulu, Oulu;
FAU - Gao, Jing
AU  - Gao J
AD  - Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and 
      Helsinki University Hospital, Helsinki;
FAU - Kanerva, Tinja
AU  - Kanerva T
AD  - Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and 
      Helsinki University Hospital, Helsinki;
FAU - Ronty, Mikko
AU  - Ronty M
AD  - HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki; and.
FAU - Toljamo, Tuula
AU  - Toljamo T
AD  - Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland.
FAU - Bergmann, Ulrich
AU  - Bergmann U
AD  - Proteomics Core Facility, Biocenter Oulu, Faculty of Biochemistry and Molecular 
      Medicine, University of Oulu, Oulu;
FAU - Mazur, Witold
AU  - Mazur W
AD  - Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and 
      Helsinki University Hospital, Helsinki;
FAU - Pulkkinen, Ville
AU  - Pulkkinen V
AD  - Heart and Lung Center, Division of Pulmonary Medicine, University of Helsinki and 
      Helsinki University Hospital, Helsinki; ville.pulkkinen@helsinki.fi.
LA  - eng
PT  - Journal Article
DEP - 20160415
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Proteome)
RN  - 0 (TGM2 protein, human)
RN  - 0 (Tripeptidyl-Peptidase 1)
RN  - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2)
RN  - EC 2.3.2.13 (Transglutaminases)
RN  - EC 3.4.14.9 (TPP1 protein, human)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Aged
MH  - Case-Control Studies
MH  - Female
MH  - GTP-Binding Proteins/*blood
MH  - Humans
MH  - Lung/*enzymology/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Protein Glutamine gamma Glutamyltransferase 2
MH  - Proteome/metabolism
MH  - Proteomics
MH  - Pulmonary Disease, Chronic Obstructive/*enzymology/pathology/physiopathology
MH  - Smoking/adverse effects/blood
MH  - Transglutaminases/*blood
MH  - Tripeptidyl-Peptidase 1
OTO - NOTNLM
OT  - chronic obstructive pulmonary disease (COPD)
OT  - difference gel electrophoresis (DIGE)
OT  - idiopathic pulmonary fibrosis (IPF)
OT  - lung tissue
OT  - two-dimensional gel electrophoresis (2-DE)
OT  - alpha-1-antitrypsin deficiency (AATD)
EDAT- 2016/04/17 06:00
MHDA- 2017/05/16 06:00
CRDT- 2016/04/17 06:00
PHST- 2016/01/13 00:00 [received]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/04/17 06:00 [entrez]
PHST- 2016/04/17 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
AID - ajplung.00021.2016 [pii]
AID - 10.1152/ajplung.00021.2016 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2016 Jun 1;310(11):L1155-65. doi: 
      10.1152/ajplung.00021.2016. Epub 2016 Apr 15.