| Project/Area Number |
17390239
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NISHIMURA Masaharu Hokkaido University, Graduate school of medicine, Professor, 大学院医学研究科, 教授 (00208224)
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| Co-Investigator(Kenkyū-buntansha) |
HIZAWA Nobuyuki Hokkaido University, Graduate school of medicine, Associate Professor, 大学院医学研究科, 助教授 (00301896)
BETSUYAKU Tomoko Hokkaido University, Hokkaido University hospital, Assistant professor, 講師 (60333605)
NASUHARA Yasuyuki Hokkaido University, Hokkaido University hospital, Assistant professor, 講師 (30322811)
ONODERA Yuya Hokkaido University, Hokkaido University hospital, Instructor, 助手 (10272064)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2005: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | COPD / emphysema / smoking / laser capture microdissection / epithelial lining fluid / microsampling / cohort / oxidative stress / Iaser capture microdissection / Laser capture microdissection / コホート研究 |
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| Research Abstract |
Epidemiological evidence suggests that cigarette smoking and aging are the two major risk factors for the development of chronic obstructive pulmonary disease (COPD). The molecular mechanism is poorly understood, in which the pathophysiology of COPD is involved. Respiratory tract is the major interface to the environment and the lung epithelium and alveolar macrophages are the first line of defense against cigarette smoke. We found that cumulative effects of aging and long-term smoking differently affected the accumulation of glutathione disulfide, an oxidized form of glutathione associated with excessive carbonyl proteins in BAL fluid, which might lead to the impaired antioxidant barrier system in the extracellular milieu in alveolar space. The lungs are anatomically complex organs. We first applied laser capture microdissection (LCM) techniques to analyze cell-specific gene expression in the smoking lungs. This study provides the molecular information of bronchiolar epithelium, macrophages, and alveolar septae in the pathogenesis of COPD. The combination of LCM with nucleotide arrays offers exciting discovery of the molecular responses of different lung cells to smoke exposure. We especially focus on the groups of genes controlling the defense mechanism, regulating the inflammation, and contributing to the maintenance of lung structure, which is related to cell apoptosis and repair. The cell-specific gene expression profile in COPD patients as well as in smoking mice could open the possibilities for the development of new therapeutic strategies, considering targeted site and the delivery of drugs.
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