2023 Fiscal Year Final Research Report
The crosstalk mechanisms between immunological cells responsible for fibrotic microenvironment and the effect of aging.
| Project/Area Number |
19K08614
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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 | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吾妻 安良太 日本医科大学, 医学部, 教授 (10184194)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | 特発性肺線維症 / 骨髄由来細胞 / macrophage polarization / MAGI2 / PTEN |
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| Outline of Final Research Achievements |
1) The bone marrow derived cells were cultured with cytokines. These cells were adoptively transferred to bleomycin-induced murine pulmonary fibrosis model, and significant attenuation of the fibrosis development was observed. The analysis of cell-surface markers revealed that these cells have properties similar to M2 macrophage.
2) A scaffolding protein MAGI2 serves as a tumor suppressor. However, the involvement of MAGI2 in fibroblast to myofibroblast is unclear. Therefore, we examined the role of MAGI2 in myofibroblast differentiation using normal human lung fibroblasts. MAGI2 expression was significantly down-regulated by TGF-β1. α-SMA expression was significantly increased upon MAGI2 depletion by siRNA, which was accompanied by AKT phosphorylation and PTEN instability. Up-regulation of α-SMA upon MAGI2 silencing was also confirmed by immunocytochemistry.
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| Free Research Field |
呼吸器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
① 骨髄由来のマクロファージ様細胞投与による肺線維症モデルマウスの線維化の改善作用は、肺線維症に対する細胞治療に発展する可能性を秘めている。今後これらの細胞の詳細な抗線維化メカニズムの検討が必要である。
② 線維化病態においてMAGI2とPTENとの関与が確認され、MAGI2の抑制により線維芽細胞から筋線維芽細胞への分化が促進されることが明らかとなった。MAGI2-PTEN axisは、肺線維化病態の新たな治療標的となることが期待される。
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