2023 Fiscal Year Final Research Report
How can the inflammasome respond to a wide variety of danger signals?
| Project/Area Number |
21K07927
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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 53010:Gastroenterology-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
馬場 良子 産業医科大学, 医学部, 准教授 (90271436)
中村 健太 産業医科大学, 医学部, 非常勤医師 (60789692)
國分 啓司 産業医科大学, 医学部, 助教 (00432740)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | PKR / 小腸上皮細胞 / インフラマソーム / 細胞死 / DSS誘導腸炎 |
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| Outline of Final Research Achievements |
This project aimed to elucidate the enhancement of the inflammasome response by PKR, and the following results were obtained. Expression of PKR, GSN, NLRP3 and active eIF-2 in the intestinal tract of mice was different in normal and induced intestinal inflammation, at different sites and during inflammatory and recovery phases; NLR3 was increased during inflammation and PKR was increased during recovery in correlation with cell proliferation. In addition, intestinal inflammation in PKR-mutant mice and mutated-PKR induced intestinal organoids resulted in a protective tendency to weight loss and inflammation and an influence on the crypt development. These indicate that PKR mutations suppress inflammasome activity and cell proliferation and, as signalling molecules, are involved in cell death and morphogenesis. The interaction between PKR and NLRP3 in these processes continues to be analysed.
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| Free Research Field |
Hisotology
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、これまでにPKRが小腸上皮細胞で重要な防御機構を果たすことを明らかとしたが、その詳細な機序は判っていない。本申請の結果より、PKRがウイルス感染時に応答するリン酸化酵素の役割のみならずシグナル分子としても機能している事および、腸炎誘導時にNLRP3とPKRが部位や時期特異的に相互作用を果たす可能性が示唆された。これらの結果は、腸上皮の機能的破綻により生じる炎症性腸疾患やNLRP3インフラマソームが関連する多くの炎症性疾患の機序解明へと繋がると考える。
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