| Project/Area Number |
20K08548
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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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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Keio University |
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Principal Investigator |
Hegab Ahmed E 慶應義塾大学, 医学部(信濃町), 共同研究員 (00507915)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | lung stem cells / lung fibrosis / high fat diet / High fat diet / Fatty acids / Fibrosis / bronchioalveolar cells / Alveolar type-2 cells / fatty a. oxidation / fibrosis / alveolar type-2 cells / Calorie restriction |
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| Outline of Research at the Start |
Recently, I showed that HFD exerts multiple potentially harmful effects on the lung. HFD induced aberrant activation of stem cells, low-grade inflammation and impairment of mitochondria. As stem cell dysfunction, lung inflammation and mitochondria are all implicated in the development of lung fibrosis, I will examine the effect of HFD on the severity and repair of lung fibrosis. I will use both animal models of lung fibrosis, and in vitro stem cell assay to identify the interaction between HFD and lung fibrosis, and to elucidate the mechanisms involved.
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| Outline of Final Research Achievements |
We have explored the effect of High fat diet on lung repair after a fibrosis-inducing injury, focusing on the effect on lung stem cells. We previously reported that High fat diet delayed the contribution of alveolar stem cells in the repair process and delayed the resolution of inflammation and fibrosis compared to the standard diet. In these new studies, we have identified the specific role of bronchioalveolar stem cells in this delay. Bronchioalveolar stem cells are rare in the lung compared to alveolar cells, so identifying their critical influence on
repair represents a major advance in our knowledge. We also examined the effect of various inhibitors of Fatty Acid Oxidation on the high fat diet-induced delay in alveolar repair and fibrosis resolution.
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| Academic Significance and Societal Importance of the Research Achievements |
Our results helps to improve our understanding of how the high fat diet negatively influence the lung repair such as after an injury that induces fibrosis. Our results explains that such negative effect of high fat diet happens because of an inhibitory effect on lung stem cells.
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