期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 310, 期 11, 页码 L1155-L1165出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00021.2016
关键词
chronic obstructive pulmonary disease (COPD); alpha-1-antitrypsin deficiency (AATD); idiopathic pulmonary fibrosis (IPF); lung tissue; two-dimensional gel electrophoresis (2-DE); difference gel electrophoresis (DIGE)
资金
- SalWe Research Program for Intelligent Monitoring of Health and Well-being (Tekes, the Finnish Funding Agency for Technology and Innovation grant) [648/10]
- EVO funding of the Helsinki University Central Hospital
- University of Helsinki
- Sigrid Juselius Foundation
- Foundation of the Finnish Anti-Tuberculosis Association
- Finnish Cultural Foundation
- Jalmari and Rauha Ahokas Foundation
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.
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