The induced RNA-binding protein, HuR targets of IL-6 mRNA and enhances its stabilization in periodontitis
Project/Area Number |
18K09599
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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 57030:Conservative dentistry-related
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Research Institution | Hiroshima University |
Principal Investigator |
Ouhara Kazuhisa 広島大学, 医系科学研究科(歯), 助教 (80550425)
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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)
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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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 歯周炎 / RNA結合タンパク質 / 歯周病源細菌 / ケルセチン / 歯周病原細菌 / 関節リウマチ / シトルリン化タンパク質 / RNA安定化タンパク質 / RNA binding protein / マウス / IL-6 |
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.
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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。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Physiologic Target, Molecular Evolution, and Pathogenic Functions of a Monoclonal Anti-Citrullinated Protein Antibody Obtained From a Patient With Rheumatoid Arthritis.2020
Author(s)
Ozawa T, Ouhara K, Tsuda R, Munenaga S, Kurihara H, Kohno H, Hamana H, Kobayashi E, Taki H, Tobe K, Sugiyama E, Muraguchi A, Kishi H.
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Journal Title
Arthritis Rheumatol.
Volume: 72
Issue: 12
Pages: 2040-2049
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Aggressive periodontitis and NOD2 variants2020
Author(s)
Mizuno Noriyoshi, Kume Kodai, Nagatani Yukiko, Matsuda Shinji, Iwata Tomoyuki, Ouhara Kazuhisa, Kajiya Mikihito, Takeda Katsuhiro, Matsuda Yukiko, Tada Yui, Ohsawa Ryosuke, Morino Hiroyuki, Mihara Keichiro, Fujita Tsuyoshi, Kawaguchi Hiroyuki, Shiba Hideki, Kawakami Hideshi, Kurihara Hidemi
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Journal Title
Journal of Human Genetics
Volume: 65(10)
Issue: 10
Pages: 841-846
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Optineurin regulates osteoblastogenesis through STAT12020
Author(s)
Mizuno Noriyoshi、Iwata Tomoyuki、Ohsawa Ryosuke、Ouhara Kazuhisa、Matsuda Shinji、Kajiya Mikihito、Matsuda Yukiko、Kume Kodai、Tada Yui、Morino Hiroyuki、Yoshimoto Tetsuya、Ueki Yasuyoshi、Mihara Keichiro、Sotomaru Yusuke
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 525(4)
Issue: 4
Pages: 889-894
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Multiple External Root Resorption of Teeth as a New Manifestation of Systemic Sclerosis-A Cross-Sectional Study in Japan.2019
Author(s)
Memida T, Matsuda S, Kajiya M, Mizuno N, Ouhara K, Fujita T, Hirata S, Yoshida Y, Sugimoto T, Nishi H, Kawaguchi H, Sugiyama E, Kurihara H.
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Journal Title
J Clin Med.
Volume: Oct 4;8(10).
Issue: 10
Pages: 1628-1628
DOI
Related Report
Peer Reviewed / Open Access
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