| Project/Area Number |
21K16457
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
Ito Homare 自治医科大学, 医学部, 助教 (60625573)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | インフラマソーム / 炎症 / サイトカイン / 細胞死 / 消化器疾患 / 腸管虚血 / パイロトーシス / 腸管虚血再灌流障害 / カスパーゼ11 / 虚血再灌流障害 / 続発性肺障害 |
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| Outline of Research at the Start |
独自に確立した信頼性・再現性の高い新規マウス腸管IR障害モデルを用いて、腸管IRにおけるCasp11及びGSDMDを介したPyroptosisの役割を検証し、その炎症・組織障害の分子機序をによる解明することを目指す。
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| Outline of Final Research Achievements |
Intestinal ischemia/reperfusion (I/R) injury causes intestinal injury and leads to inflammation and remote organ injury; however, the mechanism of intestinal I/R injury remains unclear. Here, we investigated the role of caspase-11 (Casp11) and gasdermin D (GSDMD)-mediated pyroptosis in intestinal I/R injury. Missense mutation of Casp11 markedly prolonged survival after intestinal I/R injury. Western blot analysis showed that GSDMD was expressed in various organs. Notably, the expression of GSDMD-NT (N-terminal fragment) was detected in the small intestine, indicating the activation of intestinal GSDMD. The expression of GSDME was also detected in the small intestine. These findings suggest the role of Casp11, GSDMD, and GSDME in the pathophysiology of intestinal I/R injury.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、腸管I/R障害においてCasp11およびGSDMD/GSDMEを介したPyroptosisが重要な役割を果たしていることが示された。今後の研究の発展により、腸管I/R障害の新たな分子機序の解明や新規治療法の手がかりが得られることが期待される。
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