2022 Fiscal Year Annual Research 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 / macrophages / collagen deposition / Arg2 expression |
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| Outline of Annual Research Achievements |
Pulmonary fibrosis (PF) is a serious and increasingly prevalent lung disease. In our study, we investigated the impact of Solute carrier family 15 member 3 (SLC15A3) deficiency on PF using murine models. Our findings revealed that SLC15A3 deficiency had significant positive effects on PF outcomes. It led to a reduction in collagen deposition, a key characteristic of PF, and improved respiratory function. These results indicate the potential therapeutic value of targeting SLC15A3 in PF treatment.
To gain insights into the underlying mechanisms, we employed single-cell RNA sequencing, which unveiled altered gene expression profiles, particularly enhanced expression of arginase 2 (Arg2) in SLC15A3-deficient macrophages. Arg2 is an enzyme involved in arginine metabolism and has implications for immune responses. The increased expression of Arg2 suggests a protective effect in PF associated with SLC15A3 deficiency.
In addition, our study explored the role of dietary interventions in PF. Fasting was able to enhance Arg2 expression in macrophages, which may contribute to reducing PF progression. Furthermore, SLC15A3 deficiency resulted in a significant reduction in the production of interleukin-11 (IL-11), a cytokine involved in inflammation and fibrosis. These findings suggest that targeting SLC15A3 and implementing dietary interventions, such as fasting, could hold promise as novel therapeutic approaches for PF. However, further research is needed to elucidate the precise mechanisms and to optimize the potential benefits of these strategies in managing PF effectively.
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