Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease

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 invo...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2016-06, Vol.310 (11), p.L1155-L1165
Main Authors: Ohlmeier, Steffen, Nieminen, Pentti, Gao, Jing, Kanerva, Tinja, Rönty, Mikko, Toljamo, Tuula, Bergmann, Ulrich, Mazur, Witold, Pulkkinen, Ville
Format: Article
Language:English
Subjects:
Aged
Case-Control Studies
Chronic obstructive pulmonary disease
Female
GTP-Binding Proteins - blood
Humans
Lung - enzymology
Lung - physiopathology
Lungs
Male
Mass spectrometry
Middle Aged
Proteins
Proteome - metabolism
Proteomics
Pulmonary Disease, Chronic Obstructive - enzymology
Pulmonary Disease, Chronic Obstructive - pathology
Pulmonary Disease, Chronic Obstructive - physiopathology
Smoking - adverse effects
Smoking - blood
Tissues
Transglutaminases - blood
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Summary: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.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00021.2016