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Role of red blood cells and platelets in the development of chronic inflammation of nonalcoholic steatohepatitis

Research Project

Project/Area Number 17K09437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionOsaka Metropolitan University (2022)
Osaka City University (2017-2021)

Principal Investigator

Fujii Hideki  大阪公立大学, 大学院医学研究科, 講師 (20382070)

Co-Investigator(Kenkyū-buntansha) 松原 三佐子 (佐藤三佐子 / 佐藤)  大阪公立大学, 大学院医学研究科, 特任講師 (00635120)
LE THITHANHTHUY (LE THUY)  大阪公立大学, 大学院医学研究科, 特任講師 (10572175)
松原 勤  大阪公立大学, 大学院医学研究科, 准教授 (20628698)
Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords血小板 / 赤血球 / NASH / 老化 / 脂肪肝炎 / 肝線維化 / 加齢 / 非アルコール性脂肪肝炎
Outline of Final Research Achievements

The purpose of this study was to prove the hypothesis that thrombus formation by red blood cells and platelets is involved in the formation of inflammation in the liver in non-alcoholic steatohepatitis. (1) A group of mice fed a high-fat, high-cholesterol diet (1.25%) for 16 weeks showed histopathological evidence of NASH, whereas a high-fat, high-cholesterol diet containing the anticoagulant drug, Rivaroxaban (5 mg/kg body weight/day), failed to suppress NASH. (2) Human liver biopsy tissues (N=8) were used for histological observation by electron microscopy. Detailed observation of the sinusoids revealed stasis findings, but no platelet thrombi could be found.

Academic Significance and Societal Importance of the Research Achievements

今回の研究では残念ながら自分の仮説を証明する事は出来なかった。しかし、血小板のNASH病態への関与については「血小板数が低下したNAFLD患者では指数関数的にHCC発生のリスクが上昇する」という論文を発表することが出来た(Hepatol Res. 2023;53:391-400)。血小板の形態学的観察は困難であったが、NASHの病態進展に伴い血小板が活性化されたり、多くのケモカインを放出することが明らかになりつつある。今後更なる検討が必要である。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] Multicenter, retrospective, cohort study shows platelet counts predict hepatocellular carcinoma development in patients with nonalcoholic fatty liver disease2023

    • Author(s)
      Fujii Hideki、Fujii Makoto、Iwaki Michihiro、Hayashi Hideki、Toyoda Hidenori、Oeda Satoshi、Hyogo Hideyuki、Kawanaka Miwa、Morishita Asahiro、Munekage Kensuke、et al.
    • Journal Title

      Hepatology Research

      Volume: 53 Issue: 5 Pages: 391-400

    • DOI

      10.1111/hepr.13884

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lifestyle changes during the coronavirus disease 2019 pandemic impact metabolic dysfunction–associated fatty liver disease2022

    • Author(s)
      Fujii Hideki、Nakamura Naotoshi、Fukumoto Shinya、Kimura Tatsuo、Nakano Akemi、Nadatani Yuji、Tauchi Yukie、Nishii Yuuko、Takashima Shingo、Kamada Yoshihiro、Watanabe Toshio、Kawada Norifumi
    • Journal Title

      Liver International

      Volume: 42 Issue: 5 Pages: 995-1004

    • DOI

      10.1111/liv.15158

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020090

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Validation of a two‐step approach combining serum biomarkers and liver stiffness measurement to predict advanced fibrosis2021

    • Author(s)
      Fujii Hideki、Enomoto Masaru、Fukumoto Shinya、Kimura Tatsuo、Nadatani Yuji、Takashima Shingo、Hagihara Atsushi、Uchida‐Kobayashi Sawako、Tamori Akihiro、Nishimoto Naoki、Kawada Norifumi
    • Journal Title

      JGH Open

      Volume: 5 Issue: 7 Pages: 801-808

    • DOI

      10.1002/jgh3.12590

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The FibroScan-aspartate aminotransferase score can stratify the disease severity in a Japanese cohort with fatty liver diseases2021

    • Author(s)
      Fujii Hideki、Fukumoto Shinya、Enomoto Masaru、Uchida-Kobayashi Sawako、Kimura Tatsuo、Tamori Akihiro、Nadatani Yuji、Takashima Shingo、Nishimoto Naoki、Kawada Norifumi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 13844-13844

    • DOI

      10.1038/s41598-021-93435-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease2020

    • Author(s)
      Fujii Hideki、Kawada Norifumi、Japan Study Group of NAFLD (JSG-NAFLD) Japan Study Group of NAFLD (JSG-NAFLD)
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 11 Pages: 3863-3863

    • DOI

      10.3390/ijms21113863

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HOMA-IR: An independent predictor of advanced liver fibrosis in nondiabetic non-alcoholic fatty liver disease.2019

    • Author(s)
      Fujii H, Yoneda M, et al.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: in press Issue: 8 Pages: 1-6

    • DOI

      10.1111/jgh.14595

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] マウス脂肪肝炎モデルにおける加齢の影響2019

    • Author(s)
      藤井英樹、松原三佐子、河田則文
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2024-01-30  

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