Identification of novel pulmo-modulatory factors that affect severity of obstructive lung diseases based on human epidemiological and animal model studies

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03570
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kumamoto University
• Principal Investigator: Shuto Tsuyoshi 熊本大学, 大学院生命科学研究部附属グローバル天然物科学研究センター, 准教授 (80333524)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 閉塞性肺疾患 (COPD) / 並存疾患 / GLP-1 / 糖尿病 / 肥満 / 尿酸 / メリンジョ / マクロライド系抗菌薬

Outline of Final Research Achievements

Chronic obstructive pulmonary disease (COPD) is mainly characterized by pulmonary obstruction caused by chronic mucus hypersecretion and inflammation, that ultimately lead to death from respiratory failure. We have established airway-specific overexpression of the epithelial Na+ channel β subunit in mice with C57BL/6J background (C57BL/6J-βENaC-Tg mice) as a pathophysiologically highly useful COPD mouse model. The study aimed to identify and prove pulmo-modulatory factors that affect COPD phenotype by experimental analysis of C57BL/6J-βENaC-Tg mice and a cross-sectional and a retrospective longitudinal studies with Japanese participants in a health screening program. We determined glucagon-like peptide-1 and palmitic acid as exacerbating factors, while uric acid as a protective factor specifically in female, in the pathogenesis of COPD. Moreover, we identified Melinjo seed extracts as well as macloride Azithromycin as useful agents that suppress COPD phenotypes.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

近年，COPDの新たな特徴として，種々の併存疾患 (合併症) の存在が病態形成に影響を与えることが示唆されている．併存疾患 (合併症) への着眼は，これまでにない発想を生むと考えられ，新しい側面からのCOPD治療法の開発に貢献すると考えられる．また，本研究では，「ヒト疫学-動物モデル」双方向研究を実践するものであった．既存の呼吸器疾患研究では容易に着眼することがない因子を抽出可能であり，ユニークな疾患治療標的の同定に繋がるものであり，社会的意義は極めて大きい．