2020 Fiscal Year Final Research Report

The induced RNA-binding protein, HuR targets of IL-6 mRNA and enhances its stabilization in periodontitis

Research Project

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Project/Area Number	18K09599
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57030:Conservative dentistry-related
Research Institution	Hiroshima University
Principal Investigator	Ouhara Kazuhisa 広島大学, 医系科学研究科(歯), 助教 (80550425)
Co-Investigator(Kenkyū-buntansha)	小澤龍彦富山大学, 学術研究部医学系, 准教授 (10432105) 杉山英二広島大学, 病院(医), 教授 (70179167) 藤田剛広島大学, 医系科学研究科(歯), 准教授 (80379883)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	歯周炎 / RNA結合タンパク質 / 歯周病源細菌 / ケルセチン
Outline of Final Research Achievements	RNA-binding proteins regulate mRNA stability by binding to mRNA. HuR is involved in the progression of inflammatory diseases. IL-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontitis is also an inflammatory disease caused by IL-6. The involvement of HuR in the progression of PD was assessed using in vitro and in vivo experiments. Immunohistochemistry of inflamed periodontal tissue showed strong staining of HuR. HuR mRNA and protein level was increased by Porphyromonas gingivalis (Pg) Luciferase activity was increased in HuR-over-expressing OBA-9. Down-regulation of HuR by siRNA resulted in a decrease in mRNA expression and production of IL-6. In contrast, the over-expression of HuR increased IL-6 mRNA expression and production in OBA-9. The HuR inhibitor, quercetin, suppressed bone resorption in ligature-induced periodontitis model mice as a result of down-regulation of IL-6. These results show that HuR modulates inflammatory responses by regulating IL-6.
Free Research Field	歯周治療学
Academic Significance and Societal Importance of the Research Achievements	本研究課題の成果から、歯周炎を始めとする炎症性の疾患（関節リウマチ、糖尿病、炎症性腸疾患）の炎症増悪メカニズムとしてmRNAをターゲットとした新規治験が得られた。mRNAは新型コロナウィルスに対するワクチンに利用されるなど限界広く一般にも知られている分子であるが、ケルセチンのような阻害薬を応用することで、炎症性疾患の治療に有効である可能性が示唆された。歯周炎は国民の８０％が罹患している国民病であり、高齢者はセルフケアが難しく、今後歯周炎予防にこのようなmRNA抑制をターゲットにしたものが開発可能であると考えられる。