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Research on effect of macrophage on liver fibrosis in a mouse model of hepatitis B

Research Project

Project/Area Number 17K18397
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Virology
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Sugiyama Masaya  国立研究開発法人国立国際医療研究センター, その他部局等, 副プロジェクト長 (20612427)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsB型肝炎 / 肝線維化 / マクロファージ / マウスモデル / B型肝炎ウイルス / 線維化 / 超解像 / ヒト肝細胞置換キメラマウス / 単球 / 腸内細菌 / B型肝炎ウイルス
Outline of Final Research Achievements

Single cell RNA-seq analysis was determined using human liver specimens from hepatocellular carcinomas. we enrolled patients with hepatitis B, C, and non-B non-C. Then, we determined new macrophages subset expressing specific genes in hepatitis B patients. The proportion of the new subset was upregulated in fibrosis-grade dependent manner. hepatocellular carcinomas also contained high proportion of the new subset. To confirm the localization of the new subset, the subset was accumulated around fibrosis area.

Academic Significance and Societal Importance of the Research Achievements

B型肝炎によって生じた肝障害を治療する薬剤は未だ開発されていない。高齢層に患者が多い肝炎では、その病態が進むこともあり、特に肝線維化や肝硬変を治療する薬剤の必要性は高まっている。本研究では、その肝線維化の発生機序を解析することで、病態進行に関連するキー遺伝子を複数同定するに至った。これらに対する阻害剤や治療薬が開発されることで、肝線維化等に対する治療薬の開発が進展することが期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (8 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] Prolyl Isomerase Pin1 Regulates the Stability of Hepatitis B Virus Core Protein.2020

    • Author(s)
      Nishi M, Miyakawa K, Matsunaga S, Khatun H, Yamaoka Y, Watashi K, Sugiyama M, Kimura H, Wakita T, Ryo A.
    • Journal Title

      Front Cell Dev Biol.

      Volume: 8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A prospective trial of vaccine to prevent hepatitis B virus reactivation after hematopoietic stem cell transplantation.2020

    • Author(s)
      Nishikawa K, Kimura K, Kanda Y, Sugiyama M, Kakihana K, Doki N, Ohashi K, Bae SK, Takahashi K, Ishihara Y, Mizuno I, Onishi Y, Onozawa M, Onizuka M, Yamamoto M, Ishikawa T, Inoue K, Kusumoto S, Hashino S, Saito H, Kanto T, Sakamaki H, Mizokami M
    • Journal Title

      Bone Marrow Transplant.

      Volume: .

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-Viral Effects of Interferon-λ3 on Hepatitis B Virus Infection in Cell Culture.2019

    • Author(s)
      Yamada N, Murayama A, Shiina M, Aly HH, Iwamoto M, Tsukuda S, Watashi K, Tanaka T, Moriishi K, Nishitsuji H, Sugiyama M, Mizokami M, Shimotohno K, Muramatsu M, Murata K, Kato T.
    • Journal Title

      Hepatol Res.

      Volume: .

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fairly rare small-diameter hepatocellular carcinoma with right adrenal gland metastasis having an inferior vena cava tumor thrombus: a case report.2019

    • Author(s)
      Igarashi T, Harimoto N, Matsumura N, Sugiyama M, Araki K, Yokobori T, Kosone T, Takagi H, Aishima S, Yokoo H, Shirabe K.
    • Journal Title

      Surg Case Rep.

      Volume: 5 Pages: 170-170

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Virological Factors Associated with the Occurrence of HBV Reactivation in Patients with Resolved HBV Infection Analyzed through Ultradeep Sequencing.2019

    • Author(s)
      Sakamoto K, Umemura T, Ito K, Okumura A, Joshita S, Ota M, Sugiyama M, Mizokami M, Yoneda M, Tanaka E.
    • Journal Title

      J Infect Dis.

      Volume: .

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunomodulatory mechanism of acyclic nucleoside phosphates in treatment of hepatitis B virus infection.2019

    • Author(s)
      Murata K, Tsukuda S, Suizu F, Kimura A, Sugiyama M, Watashi K, Noguchi M, Mizokami M.
    • Journal Title

      Hepatology.

      Volume: .

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine and chemokine signatures associated with hepatitis B surface antigen loss in hepatitis B patients2018

    • Author(s)
      Yoshio Sachiyo、Mano Yohei、Doi Hiroyoshi、Shoji Hirotaka、Shimagaki Tomonari、Sakamoto Yuzuru、Kawai Hironari、Matsuda Michitaka、Mori Taizo、Osawa Yosuke、Korenaga Masaaki、Sugiyama Masaya、Mizokami Masashi、Mita Eiji、Katayama Keiko、Tanaka Junko、Kanto Tatsuya
    • Journal Title

      JCI Insight

      Volume: 3 Issue: 20 Pages: 122268-122268

    • DOI

      10.1172/jci.insight.122268

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Host factors associated with HBV related HCC in Asian populations2019

    • Author(s)
      Nao Nishida, Masaya Sugiyama, Hiromi Sawai, Yong Poovorawan, Katsushi Tokunaga, Masashi Mizokami
    • Organizer
      AASLD
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phylodynamic analyses of hepatitis b virus genotype a in japan2019

    • Author(s)
      Kunikazu Hoshino, Masaya Sugiyama and Masashi Mizokami
    • Organizer
      AASLD
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Influence of Gut microbiome on liver fibrosis in chimeric mice with human hepatocytes persistently infected with hepatitis B virus2019

    • Author(s)
      Masaya Sugiyama
    • Organizer
      France-Japan Meeting on HIV and Hepatitis in Paris
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Integrated analyses of both human and HBV genome to predict HCC development2019

    • Author(s)
      Masaya Sugiyama, Nishida Nao, Katsushi Tokunaga, Mizokami Masashi
    • Organizer
      EASL Liver Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] B型肝炎ウイルス感染キメラマウスモデルでの肝線維化進展における腸内細菌叢の影響とその解析2018

    • Author(s)
      杉山真也、考藤達哉、溝上雅史
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Liver Fibrosis Induced By Gut Microbes in Chimeric Mice Model with Human Hepatocytes Perssistently infected with hepatitis B Virus.2018

    • Author(s)
      Masaya Sugiyama,Tatsuya Kanto,Masashi Mizokami
    • Organizer
      The Liver Meeting 2018(AASLD)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gut microbes mediate liver fibrosis in chimeric mice with human hepatocytes persistently infected with hepatitis B virus2018

    • Author(s)
      Masaya Sugiyama, Tatsuya Kanto, and Masashi Mizokami
    • Organizer
      THE EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] B型肝炎ウイルス感染キメラマウスモデルでの肝線維化進展における腸内細菌叢の影響とその解析2018

    • Author(s)
      杉山真也、考藤達哉、溝上雅史
    • Organizer
      日本肝臓学会総会
    • Related Report
      2017 Research-status Report

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

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