| 研究課題/領域番号 |
21K16155
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| 研究機関 | 国立研究開発法人国立国際医療研究センター |
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研究代表者 |
NguyenTien 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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| 研究期間 (年度) |
2021-04-01 – 2023-03-31
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| キーワード | Pulmonary fibrosis / Slc15a3 / Macrophage |
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| 研究実績の概要 |
Pulmonary fibrosis (PF), an intractable disease with increasing prevalence is a serious public health problem. Because the pathogenesis of PF is not well understood and therapeutic options for PF are limited, there is a need to identify potential novel targets for future treatments. Solute carrier family 15 member 3 (SLC15A3) is an amino acid/oligopeptide transporter with robust expression in innate immune cells. I found that the loss of SLC15A3 alleviated PF in murine models, bleomycin and silicosis. I found the critical role of SLC15A3 in macrophages by single-cell RNA sequence analyses, bone-marrow macrophages intra-tracheal transfer.
The findings also provided insights regarding novel mechanisms of PF alleviation, including the mechanisms underlying changes in arginine bioavailability and anti-fibrotic processes in the lungs. SLC15A3 merits further investigation for the treatment and prevention of PF.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
The study is progressing smoothly as the plan.
The first objective, the identification of cells and effective molecules that ameliorate fibrosis, was done.
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| 今後の研究の推進方策 |
The next objective of the study is mechanistic analysis of antifibrotic responses in SLC15A3-KO lung:
1. Analyses of cell-cell interactions between macrophages
and fibroblasts using lung organoids;
2. Analyses of cell-cell interactions in two-dimensional culture;
3. Analysis of the significance of the SLC15A3-autophagy axis in collagen degradation
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| 次年度使用額が生じた理由 |
In order to collect the necessary data to answer the proposed research questions, the costs for experiments such as RNA-Seq, the computer and software, the mouse maintenance, and the antibodies, probes, primer reagents, and assay kits are necessary to ensure maximum accuracy.
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