| Project/Area Number |
21K16155
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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 | National Center for Global Health and Medicine |
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Principal Investigator |
Nguyen-Tien Dat 国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (50750270)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | Pulmonary fibrosis / SLC15A3 / macrophages / collagen deposition / Arg2 expression / fibroblasts / dietary intervention / therapeutic target / Slc15a3 / Macrophage / Lung fibrosis |
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| Outline of Research at the Start |
The goal of this research proposal is to identify signaling pathways and gene networks that are critical for driving tissue repair responses in the lungs. I use a model mouse with a knock-out SLC15A3, which recovered rapidly from lung inflammation in various models of lung fibrosis. I will systematically search for cell subsets, intercellular interactions, signaling pathways, and gene networks that are critical for terminating lung inflammation and accelerating tissue repair. By accomplishing the objectives, I may provide possible therapeutic targets for treating idiopathic pulmonary fibrosis.
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| Outline of Final Research Achievements |
SLC15A3, an immune cell-expressed transporter, plays a significant role in pulmonary fibrosis (PF). Its deficiency leads to reduced collagen deposition, improved respiratory function, and increased expression of Arg2 in macrophages, indicating its involvement in the intricate molecular pathways of PF progression. Fasting has been shown to enhance Arg2 expression and suppress PF advancement. Furthermore, SLC15A3 deficiency has been associated with a decrease in IL-11 expression, potentially contributing to fibrosis. These findings highlight the potential of targeting SLC15A3 and implementing dietary interventions as innovative approaches for PF treatment, offering multiple anti-fibrotic changes in the lungs. The study expands our understanding of PF, holds promise for the development of novel therapies, and provides new perspectives for managing this challenging lung disease, ultimately improving the quality of life for individuals affected by PF.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究はSLC15A3の欠損がPFに及ぼす影響を明らかにし、科学的な理解に貢献しています。SLC15A3の欠如によるコラーゲン減少や呼吸機能の改善、マクロファージでのArg2発現増加などの結果は、PF進行に関わる分子経路を明らかにしました。これにより、標的治療法の開発への可能性が広がりました。社会的には、この研究は困難な肺線維症の管理に重要な意義を持ちます。SLC15A3を治療対象とする新たなアプローチや食事介入によるArg2増強は、PF進行を抑制する可能性があり、標準的な医療治療を補完します。これらの成果は、肺線維症患者に希望をもたらし、生活の質の向上に向けた新たな展望を提供しています.
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