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Investigation of the pathogenesis of IgA nephropathy caused by oral bacteria for the development of innovative treatment methods from the field of dentistry.

Research Project

Project/Area Number 20K10225
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionOkayama University

Principal Investigator

NAKA Shuhei  岡山大学, 大学病院, 講師 (10589774)

Co-Investigator(Kenkyū-buntansha) 仲野 和彦  大阪大学, 大学院歯学研究科, 教授 (00379083)
仲野 道代 (松本道代)  岡山大学, 医歯薬学域, 教授 (30359848)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsIgA腎症 / Streptococcus mutans / コラーゲン結合タンパク / ラット動物モデル / ラット頸静脈モデル / ラット齲蝕モデル / RNAシーケシング / IgA 腎症 / 齲蝕 / コラーゲン結合能
Outline of Research at the Start

これまでに、齲蝕の主要な病原細菌である Streptococcus mutans の中で、コラーゲン結合能を有する菌株が、感染性心内膜炎の発症、脳出血、炎症性腸炎や非アルコール性脂肪肝炎の病状の悪化を引き起こすメカニズムの一端を明らかにしてきたが、腎臓への影響に関しては未検討であった。IgA 腎症患者の唾液からコラーゲン結合能を有する S. mutans が高頻度で検出されるため、本研究では、IgA 腎症患者より分離した S. mutans を用いて、IgA 腎症発症に起因するメカニズムの一端を明らかにしたいと考えている。

Outline of Final Research Achievements

IgA nephropathy is a chronic kidney disease characterized by hematuria and proteinuria, shown by urine analysis, and IgA deposition in the glomeruli of the kidney, which can progress to end-stage renal dysfunction. However, details regarding its causes and mechanisms remain unclear. In the present study, the pathogenesis mechanism were investigated using two rat models; those that underwent jugular vein administration of the S. mutans strain and a dental caries model. A S. mutans stain isolated from the oral cavity of an IgA nephropathy patient positive for collagen binding protein was administered to rats in both models and kidney histopathological analysis was performed.
The results showed that IgA nephropathy-like nephritis developed in each of the animal models, a characteristic histopathological finding indicating IgA nephropathy in glomeruli in the kidney.

Academic Significance and Societal Importance of the Research Achievements

本研究では、実際に IgA 腎症患者の口腔から採取した菌株を使用し、動物モデル口腔内に齲蝕を誘発させることによって、一過性に細菌が体内に侵入するモデルではなく、持続的に全身へと侵入する可能性を再現するため、現実が反映できている可能性が高いと想定できるモデルであることも新たな試みの 1 つと考えている。本研究の結果、口腔細菌や歯科疾患の関連する IgA 腎症のメカニズムの一端が明らかになれば、新規治療の開発につながる可能性もあり、画期的なアプローチによって当該患者に対する利益に加えて、医療経済的にも大きな社会貢献が期待できると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (23 results)

All 2023 2022 2021 2020

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Simultaneous Presence of Campylobacter rectus and Cnm-Positive Streptococcus mutans in the Oral Cavity Is Associated with Renal Dysfunction in IgA Nephropathy Patients: 5-Year Follow-Up Analysis.2023

    • Author(s)
      Misaki T, Naka S, Nagasawa Y, Matsuoka D, Ito S, Nomura R, Matsumoto-Nakano M, Nakano K
    • Journal Title

      Nephron

      Volume: 13 Issue: 3-4 Pages: 134-143

    • DOI

      10.1159/000525511

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] cnm-positive Streptococcus mutans is associated with galactose-deficient IgA in patients with IgA nephropathy2023

    • Author(s)
      Misaki T, Naka S, Suzuki H, Lee M, Aoki R, Nagasawa Y, Matsuoka D, Ito S, Nomura R, Matsumoto-Nakano M, Suzuki Y, Nakano K.
    • Journal Title

      Plos One

      Volume: - Issue: 3 Pages: 0-0

    • DOI

      10.1371/journal.pone.0282367

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IgA Nephropathy and Oral Bacterial Species Related to Dental Caries and Periodontitis.2022

    • Author(s)
      Nagasawa Y, Misaki T, Ito S, Naka S, Wato K, Nomura R, Matsumoto-Nakano M, Nakano K.
    • Journal Title

      Int J Mol Sci.

      Volume: Jan 10;23(2) Issue: 2 Pages: 725-725

    • DOI

      10.3390/ijms23020725

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cnm of Streptococcus mutans is important for cell surface structure and membrane permeability2022

    • Author(s)
      Naka S, Matsuoka D, Goto K, Misaki T, Nagasawa Y, Ito S, Nomura R, Nakano K, Matsumoto-Nakano M
    • Journal Title

      Front Cell Infect Microbiol.

      Volume: - Pages: 994014-994014

    • DOI

      10.3389/fcimb.2022.994014

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution of periodontopathic bacterial species between saliva and tonsils2022

    • Author(s)
      Nomura Ryota, Nagasawa Yasuyuki, Misaki Taro, Ito Seigo, Naka Shuhei、Okunaka Mieko、Watanabe Maiko, Tsuzuki Kenzo, Matsumoto-Nakano Michiyo, Nakano Kazuhiko
    • Journal Title

      Odontology

      Volume: 10 Issue: 3 Pages: 719-72

    • DOI

      10.1007/s10266-022-00776-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Streptococcus mutans induces IgA nephropathy-like glomerulonephritis in rats with severe dental caries2021

    • Author(s)
      Naka S, Wato K, Misaki T, Ito S, Matsuoka D, Nagasawa Y, Nomura R, Matsumoto-Nakano M, Nakano K.
    • Journal Title

      Scientific Reports

      Volume: 11(1) Issue: 1 Pages: 5784-5784

    • DOI

      10.1038/s41598-021-85196-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and functional analysis of glutamine transporter in Streptococcus mutans2020

    • Author(s)
      Morikawa Y, Morimoto S, Yoshida E, Naka S, Inaba H, Matsumoto-Nakano M
    • Journal Title

      Journal of Oral Microbiology

      Volume: 12 Issue: 1 Pages: 1797320-1797320

    • DOI

      10.1080/20002297.2020.1797320

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions2020

    • Author(s)
      Shuhei Naka, Misaki T, Wato K, Ito S, Nagasawa Y, Nomura R, Otsugu M, Matsumoto-Nakano M, Nakano K, Kumagai H, Oshima N
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 24(12) Issue: 12 Pages: 1122-1131

    • DOI

      10.1007/s10157-020-01961-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential involvement of Streptococcus mutans possessing collagen binding protein Cnm in infective endocarditis2020

    • Author(s)
      Nomura Ryota、Otsugu Masatoshi、Hamada Masakazu、Matayoshi Saaya、Teramoto Noboru、Iwashita Naoki、Naka Shuhei、Matsumoto-Nakano Michiyo、Nakano Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 19118-19118

    • DOI

      10.1038/s41598-020-75933-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ラット IgA 腎症様腎炎モデルでの Streptococcus mutans 菌体表層タンパク Cnm の病原因子の可能性2023

    • Author(s)
      仲 周平,松岡大貴,三﨑太郎,後藤花奈,長澤康行,伊藤誓悟,野村良太,仲野道代,仲野和彦
    • Organizer
      第46回 IgA 腎症研究会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Streptococcus mutans コラーゲン結合タンパク Cnm の病原性に関する検討2022

    • Author(s)
      松岡大貴,仲 周平,後藤花奈,野村良太,仲野和彦,仲野道代
    • Organizer
      第60回日本小児歯科学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Streptococcus mutans のコラーゲン結合タンパク Cnm の構造解析2022

    • Author(s)
      松岡大貴,仲 周平,稲葉裕明,仲野道代
    • Organizer
      第41回日本小児歯科学会中四国地方会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Streptococcus mutans コラーゲン結合タンパクの IgA 腎症発症メカニズムへの関与2021

    • Author(s)
      松岡大貴,仲周平,後藤花奈,和唐薫子,野村良太,仲野和彦, 仲野道代
    • Organizer
      第59回日本小児歯科学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Investigation of Streptococcus mutans collagen-binding protein pathogenicity2021

    • Author(s)
      D. Matsuoka, S. Naka, K. Goto, M. Matsumoto-Nakano
    • Organizer
      国際歯科研究学会日本部会総会・学術大会 (JADR)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] IgA 腎症患者由来 Cnm 陽性 Streptococcus mutans の分子生物学的解析2021

    • Author(s)
      松岡 大貴, 仲 周平, 仲野 道代
    • Organizer
      第 40 回日本小児歯科学会中四国地方会
    • Related Report
      2021 Research-status Report
  • [Presentation] Prevalence of Specific Streptococcus mutans harbored by non-alcoholic steatohepatitis patients.2020

    • Author(s)
      Tabata K, Naka S, Tonomura S, Nakano K, Matsumoto-Nakano M.
    • Organizer
      The 68th Annual Meeting of Japanese Association for Dental Research (JADR)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Periodontal bacteria distribution in child with early primary tooth loss.2020

    • Author(s)
      Miyai Y, Naka S, Matsumoto-Nakano M.
    • Organizer
      The 68th Annual Meeting of Japanese Association for Dental Research (JADR)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of anticancer drugs on mouse tooth germ development.2020

    • Author(s)
      Tsunoda Y, Naka S, Okawa R, Nakano K, Matsumoto-Nakano M.
    • Organizer
      The 68th Annual Meeting of Japanese Association for Dental Research (JADR)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] IgA nephropathy-like lesion development in rat caries model.2020

    • Author(s)
      Naka S, Wato K, Misaki T, Nagasawa Y, Ito S, Nomura R, Matsumoto-Nakano M, Nakano K.
    • Organizer
      The 68th Annual Meeting of Japanese Association for Dental Research (JADR)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] う蝕ラットモデルにおける IgA 腎症様腎炎を発症する可能性2020

    • Author(s)
      三﨑太郎,清水吉貴,伊藤大介,小野雅史,鈴木由美子,仲 周平,和唐 薫子,伊藤 誓悟,野村良太,長澤康行,仲野道代,仲野和彦.
    • Organizer
      第63回日本腎臓学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Streptococcus mutans における DnaK の表層タンパク発現への影響と役割2020

    • Author(s)
      吉田衣里,松三友紀,森川優子,仲 周平,高島由紀子,仲野道代.
    • Organizer
      第58回日本小児歯科学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ラット齲蝕モデルにおける IgA 腎症様腎炎発症に関する検討2020

    • Author(s)
      仲 周平,和唐 薫子,三﨑太郎,伊藤 誓悟,野村良太,長澤康行,仲野道代,仲野和彦.
    • Organizer
      第43回 IgA 腎症研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] IgA 腎症患者の扁桃における歯周病菌レッドコンプレックスの感染率の検討2020

    • Author(s)
      長澤康行,野村良太,三﨑太郎,仲 周平,伊藤 誓悟,和唐 薫子,仲野道代,仲野和彦
    • Organizer
      第43回 IgA 腎症研究会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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