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Elucidation of NASH progression mechanism of red complex dental infection via TLR2 pathway

Research Project

Project/Area Number 16K20437
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionHiroshima University

Principal Investigator

Furusho Hisako  広島大学, 医歯薬保健学研究科(歯), 助教 (00634461)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsred complex / TLR2 / NASH / 歯性感染 / Red complex / 炎症
Outline of Final Research Achievements

In vivo experiment, crown-like structure (CLS) number and fibrosis were increased in high-fat-diet induced wild type mice groups (WT-HFD), excluding 1 group, and they were decreased in high-fat-diet induced TLR2 (TLR2KO-HFD) groups ultimately. Similarly, IL-1β mRNA expression, upregulated in WT-HFD groups, were restrained in TLR2KO-HFD groups. In vitro experiment, IL-1β and IL-6 mRNA expression were upregulated in the steatotic hepatocyte, stimulated by each red complex (Pg, Td, Tf) dead body stimulation. After the dosage of the TLR2 inhibitor, the mRNA upregulation were suppressed. It was revealed that the TLR2 pathway participated in NASH progression by the red complex odontogenic infection.

Academic Significance and Societal Importance of the Research Achievements

本研究は顎骨における歯周病原細菌感染と肝疾患の関連性を課題としている。今回の研究において作成する歯性感染モデルでは、歯周病原細菌の中のred complexを使用し、各菌単独およびその組み合わせにおいてより患者の病態を模倣したnaturalな状態を観察している。red complex歯性感染によるNASH病態増悪の機序についてTLR2の役割を明らかにしたことは、脂肪肝患者におけるTLR2を標的とした新たな治療法開発につながり、社会に還元できる有意義な研究であると考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Elevated CD14 (Cluster of Differentiation 14) and Toll-Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice.2016

    • Author(s)
      Rider D, Furusho H, Xu S, Trachtenberg AJ, Kuo WP, Hirai K, Susa M, Bahammam L, Stashenko P, Fujimura A, Sasaki H,
    • Journal Title

      Anatomical record

      Volume: Sep;299(9) Issue: 9 Pages: 1281-1292

    • DOI

      10.1002/ar.23383

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Interrelationship Between Periapical Lesion and Systemic Metabolic Disorders.2016

    • Author(s)
      Sasaki H, Hirai K, Martins CM, Furusho H, Battaglino R, Hashimoto K.
    • Journal Title

      Current pharmaceutical design

      Volume: 22(15) Pages: 2204-2215

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Phospholipase C-related catalytically inactive protein is a new modulator of thermogenesis promoted by β-adrenergic receptors in brown adipocytes2015

    • Author(s)
      Kana Oue, Jun Zhang, Kae Harada-Hada, Satoshi Asano, Yosuke Yamawaki, Masaki Hayashiuchi, Hisako Furusho, Takashi Takata, Masahiro Irifune, Masato Hirata, Takashi Kanematsu
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 8 Pages: 4185-96

    • DOI

      10.1074/jbc.m115.705723

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhanced Expression of Contractile-Associated Proteins and Ion Channels in Preterm Delivery Model Mice With Chronic Odontogenic Porphyromonas Gingivalis Infection2015

    • Author(s)
      Miyoshi H, Konishi H, Teraoka Y, Urabe S, Furusho H, Miyauchi M, Takata T, Kudo Y.
    • Journal Title

      Reprod Sci.

      Volume: なし Issue: 7 Pages: 838-846

    • DOI

      10.1177/1933719115620497

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Porphyromonas gingivalisの歯性感染は非アルコール性脂肪性肝炎の病態を増悪する2018

    • Author(s)
      宮内睦美,古庄寿子,坂本真一,高田 隆
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Porphyromonas gingivalis 歯性感染は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増悪する2017

    • Author(s)
      宮内睦美,長﨑敦洋,坂本真一,古庄寿子,髙田 隆
    • Organizer
      第60回 春季日本歯周病学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Porphyromonas gingivalis の歯性感染は非アルコール性脂肪性肝炎(NASH)の病態を増悪する2017

    • Author(s)
      宮内睦美,古庄寿子, 坂本真一, 應原和久, 栗原英見, 高田 隆
    • Organizer
      日本歯周病学会60周年記念京都大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Key roles of TLR2 in NASH progression by P.g.-odontogenic infection.2016

    • Author(s)
      Furusho H, Miyauchi M, Takata T.
    • Organizer
      第58回歯科基礎医学会学術大会
    • Place of Presentation
      北海道(札幌)
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Key roles of TLR2 in NASH progression by P.g.-odontogenic infection. Furusho H, Nagasaki A, Sakamoto S, Miyauchi M, Takata T.2016

    • Author(s)
      Furusho H, Nagasaki A, Sakamoto S, Miyauchi M, Takata T.
    • Organizer
      第64回 JADR総会・学術大会(IADR共同開催)
    • Place of Presentation
      大韓民国(ソウル)
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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