| Project/Area Number |
18K15960
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Keio University |
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Principal Investigator |
Sasaki Mamoru 慶應義塾大学, 医学部(信濃町), 共同研究員 (90573311)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 肺気腫 / 喫煙 / 肺幹細胞 / 肺胞Ⅱ型上皮細胞 / colony forming assay / Ⅱ型肺胞上皮細胞 / COPD / 幹細胞 |
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| Outline of Final Research Achievements |
In this study, we examined the effect of chronic CS on AT2 stem cells. Adult mice expressing green fluorescent protein (GFP) in their AT2 cells were exposed to CS for 5 days/week over 3-months. Histological assessment showed that CS not only induced emphysematous changes but also increased the number of AT2 cells compared to that of air-exposed lungs. Assessment of sorted GFP+/AT2 cells via the stem cell 3D organoid/colony forming assay revealed that the number and size of the colonies formed by the CS-exposed AT2 stem cells were significantly higher than those of air-exposed control AT2 cells.
AT2 stem cells respond to chronic CS exposure by activating their stem cell function, thereby proliferating and differentiating faster, and becoming more resistant to apoptosis. Disturbances in expression levels of several circadian rhythm-related genes might be involved in these changes.
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| Academic Significance and Societal Importance of the Research Achievements |
COPDは世界で最も罹患数の多い疾患の一つである。COPDはタバコ煙を主とした有害物質を長期に吸入曝露することによって生じた気道・肺の慢性炎症により引き起こされる。現在までに様々な病態に対するアプローチがなされているものの、現時点では根本的な治療はなく、病態の詳細な解析と新たな治療の確立が必要である。当研究にて長期の喫煙においてⅡ型上皮細胞の自己複製能の上昇とその関与にcircadian rythmが関連していることが示唆されたことにより、肺気腫病態の解明の一助となる可能性がある。
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