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Study on pathological progression mechanisms of non-alcoholic steatohepatitis caused by odontogenic infection of periodontal pathogen

Research Project

Project/Area Number 25462855
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphological basic dentistry
Research InstitutionHiroshima University

Principal Investigator

Miyauchi Mutsumi  広島大学, 医歯薬保健学研究院(歯), 准教授 (50169265)

Co-Investigator(Kenkyū-buntansha) Furusho Hisako  広島大学, 医歯薬保健学研究院, 助教 (00634461)
Takata Takashi  広島大学, 医歯薬保健学研究院, 教授 (10154783)
Inubushi Toshihiro  広島大学, 医歯薬保健学研究院, 助教 (30550941)
Hyogo Hideyuki  広島大学, 病院(医), 病院助教 (40397930)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords歯性感染 / Porphyromonas gingivalis / Galectin-3 / 非アルコール性脂肪性肝炎 / 線維化 / 肝星細胞 / LPS / TLR2 / TGFβ / 全身疾患 / NASH / 歯周病 / 肝線維化 / 肝癌 / porphyromonas gingivalis / 肝障害
Outline of Final Research Achievements

Non-alcoholic steatohepatitis (NASH) has the potential to progress to cirrhosis and hepatocellular carcinoma. Effective therapy has still not been established. In the present study, exacerbation mechanisms of inflammation and fibrosis caused by P.gingivalis (Pg)-odontogenic infection were examined. Upregulation of TLR2 in steatotic hepatocytes (HEP) and increase of macrophages possessing TLR2 played important roles in exacerbation of inflammation through activating TLR2 pathway by Pg-LPS. On the other hand, TGFb1, which was produced by HEP/hepatic stellate cells (HSC) with Pg-infection, promoted liver fibrosis by activating HSC. Detection of Pg in liver from NASH patients were related with high serum level of hyaluronic acid (a serum maker for liver fibrosis) and advanced fibrosis. Therefore, preventing and/or eliminating P.g. infection by dental therapy may have a beneficial impact on management of NASH.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2015 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 1 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] 歯周病原細菌と非アルコール性脂肪性肝炎のかかわり.2015

    • Author(s)
      古庄寿子, 宮内睦美, 髙田 隆
    • Journal Title

      MEDICAL TECHNOLOGY.

      Volume: 43 Pages: 902-904

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice2013

    • Author(s)
      FurushoH,Miyauchi M,Hyogo H,Inubushi T,Ao M,Ouhara K,Hisatune J,Kurihara H,Sugai M,Hayes CN,Nakahara T,Akikata H,Takahashi S,Chayama K,Takata T
    • Journal Title

      J Gastroenterol

      Volume: 48(11) Issue: 11 Pages: 1259-70

    • DOI

      10.1007/s00535-012-0738-1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 1. Porphyromonas gingivalis 歯性感染は非アルコール性脂肪性肝炎の病態進行を促進する.2013

    • Author(s)
      宮内睦美, 古庄寿子, 敖敏, 犬伏俊博, 高田 隆.
    • Journal Title

      広島歯誌

      Volume: 40 Pages: 1-6

    • Related Report
      2013 Research-status Report
  • [Presentation] TLR2 plays a key role in P.gingivalis-induced NASH progeression2015

    • Author(s)
      Furusho H, Miyauchi M, Nagasaki A, Sakamoto S, Takata T.
    • Organizer
      第63回JADR総会・学術大会
    • Place of Presentation
      博多
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] TLR2 plays a key role in P.gingivalis-induced NASH progeression.2015

    • Author(s)
      Furusho H, Miyauchi M, Nagasaki A, Sakamoto S, Takata T.
    • Organizer
      6th Hiroshima Conference on Education and Science in Dentistry
    • Place of Presentation
      Hiroshima
    • Year and Date
      2015-10-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dental infection of Porphyromonas gingivalis exacerbates pathological progression of non-alcoholic steatohepatitis (NASH).2015

    • Author(s)
      Miyauchi M, Furusho H, Nagasaki A, Sakamoto S, Ouhara K, Kurihara H, Takata T
    • Organizer
      6th Hiroshima Conference on Education and Science in Dentistry
    • Place of Presentation
      Hiroshima
    • Year and Date
      2015-10-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 歯科的治療介入はPorphyromonas gingivalis歯性感染に伴う非アルコール性脂肪性肝炎の病態進行を抑制する2015

    • Author(s)
      長﨑敦洋, 坂本真一, 古庄寿子, 宮内睦美, 髙田 隆
    • Organizer
      第54回広島県歯科医学会 第99回広島大学歯学会 日本歯科技工学会中国・四国支部第10回学術大会
    • Place of Presentation
      広島
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 歯周病は肝臓の病気に悪影響を及ぼす-歯周病原細菌の検査と歯科治療の重要性について-2015

    • Author(s)
      宮内睦美,古庄寿子,長﨑敦洋,新谷智章,栗原英見,茶山一彰,髙田 隆
    • Organizer
      第8回日口腔検査学会総会・学術大会
    • Place of Presentation
      横須賀
    • Year and Date
      2015-10-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Porphyromonas gingivalis 歯性感染はマクロファージを介して肝星細胞を活性化し非アルコール性脂肪性肝炎の病態を進行させる.2015

    • Author(s)
      長﨑敦洋, 古庄寿子, 宮内睦美, 髙田 隆
    • Organizer
      第57回歯科基礎医学会学術大会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Dental infection of Porphyromonas gingivalis (P.g.) exacerbates progression of non-alcoholic steatohepatitis; Effects of P.g. infection and P.g.-LPS on Hepatocytes2015

    • Author(s)
      Mutsumi Miyauchi, Hisako Furusho, Atsuhiro Nagasaki, Takashi Takata
    • Organizer
      IADR 2015
    • Place of Presentation
      Boston, USA
    • Year and Date
      2015-03-11 – 2015-03-14
    • Related Report
      2014 Research-status Report
  • [Presentation] The effects of Porphyromonas gingivalis infection on hepatocytes.2014

    • Author(s)
      Sakamoto S, Furusho H, Nagasaki A, Miyauchi M, Hisatsune J, Sugai M, Tahara H, and Takata T.
    • Organizer
      62nd Japanese Association of Dental Research 総会・学術大会(
    • Place of Presentation
      大阪市
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Research-status Report
  • [Presentation] Odontogenic infection of Porphyromonas gingivalis induces pathological progression of non-alcoholic steatohepatitis (NASH).2014

    • Author(s)
      Furusho H, Miyauchi M, Takata T.
    • Organizer
      第5回環太平洋アジアトピックカンファレンス
    • Place of Presentation
      神戸市
    • Year and Date
      2014-10-22 – 2014-10-23
    • Related Report
      2014 Research-status Report
  • [Presentation] Porphyromonas gingivalis (Pg)歯性感染は非アルコール性脂肪性肝炎の病態を進行させる -Pg感染やPg-LPSが肝細胞に及ぼす影響-2014

    • Author(s)
      平田真弓,古庄寿子,宮内睦美,髙田 隆
    • Organizer
      第56回歯科基礎医 学会学術大会・総会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 歯周病原細菌 Porphyromonas gingivalis の歯性感染はNASHの病態を増悪する2014

    • Author(s)
      宮内睦美,古庄寿子, 長﨑敦洋,髙田 隆
    • Organizer
      Clinical Lipid Seminar 2014
    • Place of Presentation
      広島市
    • Year and Date
      2014-09-04
    • Related Report
      2014 Research-status Report
  • [Presentation] 非アルコール性脂肪性肝炎の病態進行におよぼす歯周病の影響に関する実態調査2014

    • Author(s)
      宮内睦美,古庄寿子,長﨑敦洋,髙田 隆
    • Organizer
      第30回歯科医学を中心とした総合的な集い
    • Place of Presentation
      東京
    • Year and Date
      2014-08-30
    • Related Report
      2014 Research-status Report
  • [Presentation] Porphyromonas gingivalis 歯性感染は非アルコール性脂肪性肝炎の病態を増悪させる2014

    • Author(s)
      古庄寿子
    • Organizer
      25回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      新潟市
    • Year and Date
      2014-07-27 – 2014-07-29
    • Related Report
      2014 Research-status Report
  • [Presentation] 歯周病原細菌Porphyromonas gingivalis歯性感染はNASH病態を増悪する2014

    • Author(s)
      宮内睦美,古庄寿子,兵庫秀幸,茶山一彰,栗原英見,髙田 隆
    • Organizer
      第10回広島肝臓プロジェクト研究センターシンポジウム
    • Place of Presentation
      広島市
    • Year and Date
      2014-07-05
    • Related Report
      2014 Research-status Report
  • [Presentation] Porphyromonas gingivalis 歯性感染は非アルコール性脂肪性肝炎(NASH)の病態進行の増悪因子である.2013

    • Author(s)
      宮内睦美, 古庄寿子, 高田 隆.
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 15. Pathological progression of non-alcoholic steatohepatitis is exacerbated by dental Infection of Porphyromonas gingivalis.2013

    • Author(s)
      Sakamoto S, Hirata M, Furusho H, Inubushi, T, Miyauchi M, Takata T
    • Organizer
      5th Hiroshima Conference on Education and Science in Dentistry
    • Place of Presentation
      広島市
    • Related Report
      2013 Research-status Report
  • [Presentation] P.gingivalisの歯性感染は非アルコール性脂肪肝炎(NASH)のリスクファクターである.

    • Author(s)
      高田 隆
    • Organizer
      日本歯科人間ドック学会 第16回学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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