2021 Fiscal Year Research-status Report
Elucidation of tissue-repair response in lung fibrosis by focusing on the amino acid transporter SLC15A3
| Project/Area Number |
21K16155
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
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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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | Pulmonary fibrosis / Slc15a3 / Macrophage |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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| Causes of Carryover |
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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