| Project/Area Number |
18K09473
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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 56070:Plastic and reconstructive surgery-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Akiko Yano 東北大学, 医学系研究科, 非常勤講師 (70612224)
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| Co-Investigator(Kenkyū-buntansha) |
菅野 恵美 東北大学, 医学系研究科, 准教授 (10431595)
丹野 寛大 東北大学, 医学系研究科, 助教 (10755664)
高木 尚之 東北大学, 医学系研究科, 助教 (30569471)
館 正弘 東北大学, 医学系研究科, 教授 (50312004)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 慢性創傷 / 好中球 / ネトーシス / C型レクチン受容体 / Dectin（デクチン）-2 / 糖尿病性足壊疽 / ネトーシス (NETosis) / 感染 |
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| Outline of Final Research Achievements |
C-type lectin receptors recognize microbial polysaccharides. The C-type lectin receptors such as dendritic cell-associated C-type lectin (Dectin)-1 and Dectin-2, which are triggered by β-glucan and α-mannan, respectively, contribute to upregulation of the inflammatory response. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Full-thickness wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency and those of β-glucan or α-mannan administration were examined. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation. We found that Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性足壊疽など慢性創傷は、血流不全(血栓)、感染症に加え、好中球の機能異常が関与する複合的な病態であり、糖尿病患者の25%が生涯に足壊疽を形成することが報告されている。これまで、血流不全、感染症に対する治療法は様々検討されているが、好中球の機能異常に関する研究、治療法は発展途上にあった。
本研究成果により、難治性皮膚潰瘍の治癒遅延に好中球のネトーシスが関与し、さらにその現象にC型レクチン受容体であるDectin-2の関与が明らかになったことから、今後、Dectin-2阻害によるネトーシス制御、皮膚潰瘍治療法への応用が視野に入り、社会的意義は非常に高い。
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