Identification of novel pulmo-modulatory factors that affect severity of obstructive lung diseases based on human epidemiological and animal model studies
Project/Area Number |
17H03570
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Laboratory animal science
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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)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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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 / COPD / ENaC / 上皮細胞 / 閉塞性肺疾患 / 疫学解析 / HTS / 疾患モデル / 薬理学 |
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.
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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.
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Azithromycin Inhibits Constitutive Airway Epithelial Sodium Channel Activation <i>in Vitro</i> and Modulates Downstream Pathogenesis <i>in Vivo</i>2020
Author(s)
Haruka Fujikawa, Taise Kawakami, Ryunosuke Nakashima, Aoi Nasu, Shunsuke Kamei, Hirofumi Nohara, Yuka Eto, Keiko Ueno-Shuto, Toru Takeo, Naomi Nakagata, Mary Ann Suico, Hirofumi Kai, Tsuyoshi Shuto.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 43
Issue: 4
Pages: 725-730
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2020-04-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions.2020
Author(s)
K. Oniki, T. Kawakami, A. Nakashima, K. Miyata, T. Watanabe, H. Fujikawa, R. Nakashima, A. Nasu, Y. Eto, N. Takahashi, H. Nohara, M. Ann Suico, S. Kotani, Y. Obata, Y. Sakamoto, Y. Seguchi, J. Saruwatari, T. Imafuku, H. Watanabe, T. Maruyama, H. Kai, T. Shuto
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Journal Title
Scientific reports
Volume: 10
Issue: 1
Pages: 4313-4313
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Curcumin Down-Regulates Toll-Like Receptor-2 Gene Expression and Function in Human Cystic Fibrosis Bronchial Epithelial Cells2019
Author(s)
Chaudhary N, Ueno-Shuto K, Ono T, Ohira Y, Watanabe K, Nasu A, Fujikawa H, Nakashima R, Takahashi N, Suico MA, Kai H, Shuto T
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 3
Pages: 489-495
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-03-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Integrative expression analysis identifies a novel interplay between CFTR and linc-SUMF1-2 that involves CF-associated gene dysregulation2019
Author(s)
Kamei S, Maruta K, Fujikawa H, Nohara H, Ueno-Shuto K, Tasaki Y, Nakashima R, Kawakami T, Eto Y, Suico MA, Suzuki S, Gruenert DC, Li JD, Kai H, Shuto T.
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 509
Issue: 2
Pages: 521-528
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A split-luciferase-based trimer formation assay as a high-throughput screening platform for therapeutics in Alport syndrome2018
Author(s)
Kohei Omachi, Misato Kamura, Keisuke Teramoto, Haruka Kojima, Tsubasa Yokota, Shota Kaseda, Jun Kuwazuru, Ryosuke Fukuda, Kosuke Koyama, Shingo Matsuyama, Keishi Motomura, Tsuyoshi Shuto, Mary Ann Suico and Hirofumi Kai.
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Journal Title
Cell Chem Biol.
Volume: 印刷中
Issue: 5
Pages: 634-643.e4
DOI
Related Report
Peer Reviewed
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[Journal Article] Zinc Deficiency via a Splice Switch in Zinc Importer ZIP2/SLC39A2 Causes Cystic Fibrosis-Associated MUC5AC Hypersecretion in Airway Epithelial Cells2018
Author(s)
Kamei S, Fujikawa H, Nohara H, Ueno-Shuto K, Maruta K, Nakashima R, Kawakami T, Matsumoto C, Sakaguchi Y, Ono T, Suico MA, Boucher RC, Gruenert DC, Takeo T, Nakagata N, Li JD, Kai H, Shuto T.
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Journal Title
EBioMedicine.
Volume: 27
Pages: 304-316
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Therapeutic potential of metformin in novel COPD mouse model with diffuse-type emphysema2019
Author(s)
Ryunosuke Nakashima, Hirofumi Nohara, Shunsuke Kamei, Haruka Fujikawa, Kasumi Maruta, Taisei Kawakami, Yuka Eto, Noriki Takahashi, Aoi Nasu, Mary-Ann Suico, Hirofumi Kai, Tsuyoshi Shuto
Organizer
ASCB|EMBO 2019 meeting
Related Report
Int'l Joint Research
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[Presentation] 慢性閉塞性肺疾患様気道上皮細胞における FABP5 の発現上昇の病態生理学的意義2018
Author(s)
江藤 結花, 野原 寛文, 亀井 竣輔, 藤川 春花, 丸田 かすみ, 中嶋 竜之介, 川上 太聖, 高橋 宜暉, メリーアン スイコ, 甲斐 広文, 首藤 剛
Organizer
日本薬学会 第138年会
Related Report
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[Presentation] LNC-SOX4-2:1 LINKS CFTR DYSREGULATION AND TLR2 UP-REGULATION IN AIRWAY EPITHELIAL CELLS2017
Author(s)
Shunsuke Kamei, Kasumi Maruta, Hirofumi Nohara, Haruka Fujikawa, Ryunosuke Nakashima, Keiko Ueno-Shuto, Yukihiro Tasaki, Mary Ann Suico, Dieter C. Gruenert, Hirofumi Kai, Tsuyoshi Shuto
Organizer
31st Annual North American Cystic Fibrosis Conference
Related Report
Int'l Joint Research
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