| Project/Area Number |
21K07073
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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 49070:Immunology-related
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨髄異形成症候群 / HMGA2 / 器質化肺炎 / MDS |
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| Outline of Research at the Start |
HMGA2 高発現がMDSにおいて器質化肺炎を引き起こす機序を解明する。まずモデルマウスの気管支周囲に浸潤する免疫細胞を同定する。特定した免疫細胞集団で遺伝子発現解析を行い、免疫応答異常と関連する特徴を見出し、それが免疫応答異常に寄与するか解析する。またモデル動物の免疫応答異常を試験管レベルで再現し、器質化肺炎治療薬の探索に役立てることを目指す。
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| Outline of Final Research Achievements |
Myelodysplastic syndromes (MDS) often involve complications such as noninfectious pneumonia and autoimmune diseases. HMGA2 is known as a factor that exacerbates the pathology in hematopoietic neoplasms, and its high expression has been reported in cases of myelofibrosis and MDS. However, the involvement of HMGA2 overexpression in the pathogenesis of MDS was remained unclear. We generated an HMGA2 overexpression MDS model mice that reflects clinical findings. Analyses of this model revealed that HMGA2 overexpression contributes to platelet activation. Activated platelets interact with MDS clone-derived neutrophils, which exhibit increased susceptibility to cell death, thereby contributing to the development of noninfectious pneumonia.
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| Academic Significance and Societal Importance of the Research Achievements |
MDS患者におこる非感染性肺炎などの合併症は、生活の質を著しく低下させます。本研究をもとに血小板-好中球複合体形成を標的とした新たな治療法が開発されることで、患者の生活の質が向上する可能性があります。また治療が効率化されることで長期的には医療費の削減につながる可能性があります。
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