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The effect of myokines on the progression of arteriosclerosis associated with periodontal disease

Research Project

Project/Area Number 21K16981
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionAichi Gakuin University

Principal Investigator

Miyabe Megumi  愛知学院大学, 歯学部, 講師 (70734929)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords動脈硬化 / 歯周病 / マイオカイン / 慢性炎症 / 歯周炎
Outline of Research at the Start

多くの研究から炎症が動脈硬化の発症、進展に関与する事が示唆されており、疫学調査から慢性炎症性疾患の歯周病が、動脈硬化性心血管障害と関連する事が報告されてきたが、詳細な機序については解明されていない。申請者は、follistatin-like 1(Fstl-1)が血管平滑筋細胞の増殖や遊走、血管障害後の新生内膜形成を抑制する事を明らかにした。本研究では、①歯周炎が動脈硬化の発症や進展に関わるメカニズムを明確にし、歯周病治療による動脈硬化の予防や進展抑制の方策を確立する。②マイオカインであるirisinが動脈硬化に及ぼす影響を解明することにより、動脈硬化の新たな治療手段や予防法の確立を目指す。

Outline of Final Research Achievements

In this study, we showed that human aortic smooth muscle cells (HASMCs) were stimulated with lipopolysaccharide (Pg-LPS) derived from the periodontal pathogen Porphyyomonas gingivalis, and that proliferation and migration of HASMCs were significantly increased. We demonstrated that the proliferation of HASMCs stimulated with Pg-LPS involves a signaling pathway mediated by ERK in a manner independent of MyD88 from TLR4, and that migration involves a pathway mediated by JNK and p38 from TLR4/MyD88, and a pathway mediated by ERK in a manner independent of MyD88 from TLR4. Furthermore, administration of irisin suppressed the proliferation and migration of HASMCs stimulated with Pg-LPS.

Academic Significance and Societal Importance of the Research Achievements

本研究において慢性炎症性疾患である歯周炎の存在が動脈硬化の発症や進展に関わるメカニズムの一部を明らかにした。それにより歯周病治療による動脈硬化の予防や進展抑制の可能性を示唆することができた。また、マイオカインの一つであるIrisinが歯周病原細菌由来のLPS刺激による血管平滑筋の増殖と遊走を抑制することを示したことで動脈硬化の新たな治療手段や予防法の確立につなげることが可能になる。また、動脈硬化も歯周病も世界中で多くの人々が罹患する疾患であり、特に動脈硬化性疾患によって多くの人の生命予後が左右されることから今回の研究成果はこれからの世界中の多くの患者の生命予後を改善する可能性を持っている。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (12 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Impacts of Glucose-Dependent Insulinotropic Polypeptide on Orthodontic Tooth Movement-Induced Bone Remodeling2022

    • Author(s)
      Yamauchi Taisuke、Miyabe Megumi、Nakamura Nobuhisa、Ito Mizuho、Sekiya Takeo、Kanada Saki、Hoshino Rina、Matsubara Tatsuaki、Miyazawa Ken、Goto Shigemi、Naruse Keiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 16 Pages: 8922-8922

    • DOI

      10.3390/ijms23168922

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Salivary gland polymorphous adenocarcinoma: Clinicopathological features and gene alterations in 36 Japanese patients2022

    • Author(s)
      Fukumura Masahiro、Ishibashi Kenichiro、Nakaguro Masato、Kirita Tadaaki、Takata Takashi、Morinaga Shojiroh、Maeda Hatsuhiko、Warnakulasuriya Saman、Miyabe Satoru、Nagao Toru, et al.
    • Journal Title

      Journal of Oral Pathology & Medicine

      Volume: 51 Issue: 8 Pages: 710-720

    • DOI

      10.1111/jop.13336

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Porphyromonas gingivalis Lipopolysaccharides Promote Proliferation and Migration of Human Vascular Smooth Muscle Cells through the MAPK/TLR4 Pathway2022

    • Author(s)
      Miyabe Megumi、Nakamura Nobuhisa、Saiki Tomokazu、Miyabe Satoru、Ito Mizuho、Sasajima Sachiko、Minato Tomomi、Matsubara Tatsuaki、Naruse Keiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 1 Pages: 125-125

    • DOI

      10.3390/ijms24010125

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased expression of angiopoietin‐like protein 4 regulates matrix metalloproteinase‐13 expression in <i>Porphyromonas gingivalis</i> lipopolysaccharides‐stimulated gingival fibroblasts and ligature‐induced experimental periodontitis2022

    • Author(s)
      Kondo Shun、Kojima Kento、Nakamura Nobuhisa、Miyabe Megumi、Kikuchi Takeshi、Ohno Tasuku、Sawada Noritaka、Minato Tomomi、Saiki Tomokazu、Ito Mizuho、Sasajima Sachiko、Matsubara Tatsuaki、Mitani Akio、Naruse Keiko
    • Journal Title

      Journal of Periodontal Research

      Volume: 58 Issue: 1 Pages: 43-52

    • DOI

      10.1111/jre.13067

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Case Report: Non-episodic Angioedema With Eosinophilia in a Young Lactating Woman.2021

    • Author(s)
      Mizuho Hirmatsu-Ito, Nobuhisa Nakamura, Megumi Miyabe, Tatsuaki Matsubar, Keiko Naruse
    • Journal Title

      Front Immunol

      Volume: 12 Pages: 627360-627360

    • DOI

      10.3389/fimmu.2021.627360

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Effects of Insulin on Immortalized Rat Schwann Cells, IFRS12021

    • Author(s)
      Tomokazu Saiki, Nobuhisa Nakamura, Megumi Miyabe, Mizuho Ito, Tomomi Minato, Kazunori Sango, Tatsuaki Matsubara, Keiko Naruse
    • Journal Title

      Int J Mol Sci

      Volume: 22 Issue: 11 Pages: 5505-5505

    • DOI

      10.3390/ijms22115505

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sustainable Effects of Human Dental Pulp Stem Cell Transplantation on Diabetic Polyneuropathy in Streptozotocine-Induced Type 1 Diabetes Model Mice.2021

    • Author(s)
      Masaki Hata, Maiko Omi, Yasuko Kobayashi, Nobuhisa Nakamura, Megumi Miyabe, Mizuho Ito, Tasuku Ohno, Yuka Imanishi, Tatsuhito Himeno, Hideki Kamiya, Jiro Nakamura, Hitoshi Miyachi, Shogo Ozawa, Ken Miyazawa, Akio Mitani, Toru Nagao, Shigemi Goto, Jun Takebe, Tatsuaki Matsubara, Keiko Naruse
    • Journal Title

      Cells

      Volume: 10 Issue: 9 Pages: 2473-2473

    • DOI

      10.3390/cells10092473

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] β-Aminoisobutyric acid, L-BAIBA, protects PC12 cells from hydrogen peroxide-induced oxidative stress and apoptosis via activation of the AMPK and PI3K/Akt pathway2021

    • Author(s)
      Tomomi Minato, Nobuhisa Nakamura, Tomokazu Saiki, Megumi Miyabe, Mizuho Ito, Tatsuaki Matsubara, Keiko Naruse
    • Journal Title

      IBRO Neurosci Rep

      Volume: 12 Pages: 65-72

    • DOI

      10.1016/j.ibneur.2021.12.001

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] メタボリックシンドローム合併歯周炎に対するGLP-1受容体作動薬の効果-Zucker fattyラットを用いた検討-.2023

    • Author(s)
      近藤 駿、澤田憲孝、小島健人、笹島沙知子、湊 智美、中村信久、菊池 毅、鈴木佑基、宮部 愛、伊藤瑞穂、三谷章雄、成瀬桂子
    • Organizer
      第36回日本糖尿病・肥満動物学会年次学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] DPNcheckで測定した腓腹神経伝導速度の有用性の検討2023

    • Author(s)
      伊藤瑞穂、中村信久、小林泰子、宮部愛、笹島沙知子、成瀬桂子
    • Organizer
      第66回日本糖尿病学会年次学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯周炎におけるANGPTL4の関与と高グルコースの影響2023

    • Author(s)
      近藤駿、小島健人、中村信久、宮部愛、菊池毅、大野 祐、澤田憲孝、湊 智美、斉木智一、伊藤瑞穂、笹島沙知子、松原達昭、三谷章雄、成瀬桂子
    • Organizer
      第66回日本糖尿病学会年次学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Extrapancreatic effects of GIP on bone.2023

    • Author(s)
      Yamauchi T, Nakamura N, Miyabe M, Ito M, Hosino R, Kanada S, Sekiya T, Miyazawa K, Goto S, Naruse K
    • Organizer
      American Diabetes Association’s 83rd Scientific Sessions
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The involvement of ANGPTL4 in periodontitis and the influence of high glucose.2023

    • Author(s)
      Kondo S, Kojima K, Nakamura N, Miyabe M, Kikuchi T, Ohno T, Sawada N, Minato T, Saiki T, Ito M, Sasajima S, Matsubara T, Mitani A, Naruse K
    • Organizer
      American Diabetes Association’s 83rd Scientific Sessions
    • Related Report
      2023 Annual Research Report
  • [Presentation] マイオカインによる歯周炎が関与する動脈硬化の進展抑制に対する効果と歯周組織の再生における効果の検討.2023

    • Author(s)
      宮部 愛、中村信久、伊藤瑞穂、笹島佐知子、成瀬桂子
    • Organizer
      愛知学院大学歯学会第102回学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Impacts of Glucose-Dependent Insulinotropic Polypeptide on Bone Remodeling.2023

    • Author(s)
      Yamauchi T, Nakamura N, Miyabe M, Ito M, Hosino R, Kanada S, Miyazawa K, Goto S, Naruse K
    • Organizer
      IDF-WPR Congress 2023 / 15thAASD Scientific Meeting in Conjunction with JADEC Annual Scientific Meeting
    • Related Report
      2023 Annual Research Report
  • [Presentation] Transplantation of dental pulp stem cells ameliorates hindlimb skeletal muscle atrophy and peripheral nerve dysfunction in diabetic rats2023

    • Author(s)
      Naruse K, Omi M, Hata M, Nakamura N, Miyabe M, Sasajima S, Ozawa S, Takebe J, Matsubara T.
    • Organizer
      33rd Annual Meeting of the Diabetic Neuropathy Study Group
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯周病の存在が動脈硬化促進に影響を及ぼす可能性についての検討2022

    • Author(s)
      宮部愛、中村信久、伊藤瑞穂、斎木智一、松原達昭、成瀬桂子
    • Organizer
      第54回動脈硬化学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] マイオカインによる歯周炎が関与する動脈硬化の進展抑制に対する効果と再生医療への展望2022

    • Author(s)
      宮部愛、中村信久、伊藤瑞穂、斎木智一、松原達昭、成瀬桂子
    • Organizer
      第100回愛知学院大学歯学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 歯周病原細菌由来LPSは血管平滑筋細胞の増殖・遊走を促進する2021

    • Author(s)
      宮部 愛、中村 信久、伊藤 瑞穂、斎木 智一、松原 達昭、成瀬 桂子
    • Organizer
      第36回糖尿病合併症学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 歯周病が動脈硬化の促進に及ぼす可能性についての検討2021

    • Author(s)
      宮部 愛、中村 信久、伊藤 瑞穂、斎木 智一、松原 達昭、成瀬 桂子
    • Organizer
      第64回秋季日本歯周病学会学術大会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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