2021 Fiscal Year Final Research Report
Cell damage suppression mechanism via cell polarity control by a novel inflammatory response signal pathway
Project/Area Number |
19K07505
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49030:Experimental pathology-related
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Research Institution | Tottori University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 上皮バリア / 細胞極性 / aPKC / 炎症 / タイトジャンクション |
Outline of Final Research Achievements |
In this study, we aimed to clarify whether the disruption of epithelial barrier function is suppressed by a regulation of cell polarity regulator, aPKC activity. In cultured epithelial cell, radical generators or LPS induced aPKC activation revealed that suppression of the loss of intercellular adhesion structures remove to calcium in culture medium. This effect was inhibited by inflammasome inhibitor, caspase-1. On the other hand, analysis using mouse models of liver and lung injury confirmed that pretreatment with low concentrations of LPS protected disturbance of intercellular adhesion structures in those tissues. These results suggest that activation of aPKC prior to cell injury exerts a protective effect on intercellular adhesion structures through activation of inflammasomes.
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Free Research Field |
細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
インフラマソームの過剰な活性化は、様々な炎症性疾患の発症に関わっている。本申請は、従来とは異なる新規炎症応答シグナル経路によって上皮バリア機能が強化され、過剰な炎症(急性炎症)による細胞・組織傷害を抑制(保護)する事が明らかとなった。 上皮バリア機能の異常を伴う炎症性腸疾患、癌などに対して本研究課題で得られた結果は、それら病態の治療法や予防法の確立の新たな分子基盤として提示できその波及効果は大きい。
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