| Project/Area Number |
18K08893
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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 55060:Emergency medicine-related
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| Research Institution | Tokyo Medical University (2019-2023)
Kumamoto University (2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
江嶋 正志 熊本大学, 病院, 助教 (20718316)
早田 学 熊本大学, 病院, 助教 (30646120)
鷺島 克之 熊本大学, 病院, 講師 (40336235)
徳永 健太郎 熊本大学, 病院, 助教 (50751335)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | microRNA / Sepsis / SIRS / Inflammation / microRNA-21 / inflammation / miR-21 / PDCD4 / PTEN / PDCD-4 / 敗血症 / Innate Immunity / Ｓｅｐｓｉｓ / ｍｉｃｒｏＲＮＡ / Ｉｎｆｌａｍｍａｔｉｏｎ / Infection |
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| Outline of Final Research Achievements |
There is currently no effective treatment for sepsis, and the development of new diagnostic and therapeutic methods is required. MicroRNAs (miRs) are stable within exosomes and are responsible for intercellular signaling. In monocytes from patients under invasive care and in monocyte cell lines, miR21 increased in a concentration- and time-dependent manner upon stimulation with LPS or cytokines. The specificity of PDCD4, a target gene of miR21, was elucidated using a luciferase assay. Microarrays of miRs in exosomes in the serum of patients with sepsis and SIRS were performed, and multiple miRs were found to be involved in a complex manner. It is suggested that in sepsis, miR21 may negatively regulate acute inflammation, in part, via PDCD-4.
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| Academic Significance and Societal Importance of the Research Achievements |
敗血症性ショックの死亡率は30～40％と未だに高く治療法は未だ決定的なものはない。本研究において、敗血症にかかわるmicroRNAは数多く存在し、複雑に関わっていることが改めて明らかにされた。その中で、microRNA-21がSIRSによる炎症時に増加することが明らかとなっていきたが、その役割について不明な中、microRNA-21の標的遺伝子の一つである細胞死抑制機能を有するPDCD4が、炎症の促進因子であることが報告された。このことにより、microRNA-21が炎症制御のためのNegative Feedbackによる発現であることが示唆され、今後の検証により創薬の可能性が期待される。
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