| Project/Area Number |
17K08545
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Kyoto Pharmaceutical University (2018-2019)
Kyoto Prefectural University of Medicine (2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中張 隆司 京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (20189020)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 粘液線毛クリアランス / ｐＨ / クロライドイオン / 気道上皮線毛細胞 / 高ＣO2 / pH / 気道線毛細胞 / pH制御イオン輸送体 / 気道線毛運動 / ＣOPD / COPD |
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| Outline of Final Research Achievements |
In patients with chronic obstructive pulmonary disease (COPD), hypercapnia is associated with the aggravation of obstructive ventilatory impairment. We hypothesized that hypercapnia may decrease airway ciliary clearance through changes in airway ciliary cell pHi, which is the cause of frequent airway infections. Differentiation of airway ciliated cells was induced from human-derived primary cultured cells, and ciliary movement and transepithelial ion transport (particularly chloride ion transport), which are indicators of mucociliary clearance, were evaluated in a high CO2 environment (10% CO2). It was clarified that the high CO2 environment lowers the intracellular pH and chloride concentration of airway epithelial cells, resulting in a decrease in ciliary motility and a decrease in transepithelial ion transport.
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| Academic Significance and Societal Importance of the Research Achievements |
COPD患者の気道における高CO2環境の環境は、細胞内ｐHの低下やクロライドイオンの低下をもたらすことが明らかとなった。また、それに伴う線毛細胞における線毛運動の低下と、クロライド分泌の低下による気道上皮被服液の低下をもたらし、さらには気道被覆液のｐHの低下をもたらすことを明らかとした。このことは粘液線毛クリアランスの低下を誘導し気道感染のリスクを高めていると考えられた。粘液線毛クリアランスの低下に対して重炭酸イオンの重要性も明らかとなり、今後、細胞膜上での重炭酸イオン輸送体をターゲットとした創薬開発の重要性が示唆された。
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