Proteomic analysis in lung tissue of smokers and COPD patients.
BACKGROUND
Although cigarette smoking is the most important risk factor for COPD, COPD develops in only a minority of smokers, suggesting a significant genetic role. To solve the underlying pathophysiologic mechanism, it is critical to understand genes and their final product, ie, proteins. We investigated the exclusive proteins from the lung tissues obtained from COPD patients using proteomics.


METHODS
Nontumorous lung tissue specimens were obtained from patients who underwent surgery for lung cancer. We included 22 subjects: nonsmokers (n = 8), smokers without COPD (healthy smokers, n = 7), and smokers with COPD (n = 7). Proteins were separated from their spots with two-dimensional polyacrylamide gel electrophoresis and examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). To validate the proteins from the above procedures, Western blotting and immunohistochemistry were conducted.


RESULTS
Twelve protein spots from COPD group significantly increased or decreased compared with the other two groups were chosen for MALDI-TOF-MS analysis. Eight proteins were up-regulated in the COPD group as compared with the nonsmokers. Meanwhile, five proteins from the COPD group were up-regulated and five were down-regulated when compared with healthy smokers. Of these, matrix metalloproteinase (MMP)-13 and thioredoxin-like 2 were significantly increased in the COPD patients by Western blot and immunohistochemistry. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes; however, thioredoxin-like 2 was primarily seen in the bronchial epithelium.


CONCLUSIONS
MMP-13 and thioredoxin-like 2 in lungs increased in patients with COPD. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes. In contrast, thioredoxin-like 2 was primarily seen in the bronchial epithelium.
Lee
Eun Joo
EJ
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul.
In
Kwang Ho
KH
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul. Electronic address: khin@kumc.or.kr.
Kim
Je Hyeong
JH
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Ansan.
Lee
Sang Yeub
SY
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul.
Shin
Chol
C
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Ansan.
Shim
Jae Jeong
JJ
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul.
Kang
Kyung Ho
KH
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul.
Yoo
Se Hwa
SH
Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul.
Kim
Chul Hwan
CH
Department of Pathology, Korea University College of Medicine, Seoul.
Kim
Han-Kyeom
HK
Department of Pathology, Korea University College of Medicine, Seoul.
Lee
Sang Hoon
SH
Department of Anatomy, Korea University College of Medicine, Korea University College of Medicine, Seoul, Korea.
Uhm
Chang Sub
CS
Department of Anatomy, Korea University College of Medicine, Korea University College of Medicine, Seoul, Korea.