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Enhancement effect by bone marrow cell transplantation and macrophage regulation by S-allyl glutathione in rat liver fibrosis

Research Project

Project/Area Number 17K01858
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionKyoto Prefectural University

Principal Investigator

Minamiyama Yukiko  京都府立大学, 生命環境科学研究科, 教授 (00362989)

Co-Investigator(Kenkyū-buntansha) 竹村 茂一  大阪市立大学, 大学院医学研究科, 講師 (00322363)
岡 真優子  京都府立大学, 生命環境科学研究科, 准教授 (40347498)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肝硬変治療 / 活性酸素 / マクロファージ / 骨髄細胞移入 / 肝線維化治療 / マクロファージ分極制御 / 分極制御 / 肝線維化 / 骨髄細胞移入療法 / S-アリルグルタチオン / 肝硬変 / GFPラット / 骨髄細胞移植 / アリルシステイン / マクロファージ分極 / 生活習慣病 / 臓器線維症
Outline of Final Research Achievements

Although carbon tetrachloride liver fibrosis in rats was significantly suppressed by both bone marrow cell transfer (BMC) and SAG administration, the difference in the mechanism was not clear. SAG was found to be involved in polarization of macrophages (Mφ). From the results of DNA array with different types of Mφ polarization, changes in some same proteins were also confirmed in this model. SAG suppressed the ROS production system by TGF-β. However, BMC had no effect. From the above findings, co-administration of SAG and BMC transfer can effectively suppress hepatic fibrosis via the different mechanism. This clinical application is expected to reduce the burden on the patient and treat against hepatic fibrosis by different mechanisms.

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪性肝疾患(NAFLD)や脂肪性肝炎(NASH)患者は1000 万人以上であり、90%以上が生活習慣病を合併している。この患者は数十年で3~5 割が肝硬変に、その数%が肝がんに進行する。この肝硬変の治療は困難であり、安全な治療法の開発が急務である。本研究において、骨髄細胞移入と酸化ストレスを抑制しMφを制御できるS-アリルグルタチオンの投与という異なる機序の治療を組み合わせることで患者負担が少なく有効な治療法となる可能性を提案することができたと考える。

Report

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

    (6 results)

All 2018 2017

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

  • [Journal Article] Pirfenidone suppresses polarization to M2 phenotype macrophages and the fibrogenic activity of rat lung fibroblasts.2018

    • Author(s)
      Toda M, Mizuguchi S, Minamiyama Y, Yamamoto-Oka H, Aota T, Kubo S, Nishiyama N, Shibata T, Takemura S.
    • Journal Title

      J Clin Biochem Nutr.

      Volume: 63 Pages: 58-65

    • DOI

      10.1016/j.ejphar.2019.02.006

    • NAID

      130007387138

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] S-allyl-glutathione improves experimental liver fibrosis by regulating Kupffer cell activation in rats.2017

    • Author(s)
      Takemura S, Azuma H, Osada-Oka M, Kubo S, Shibata T, Minamiyama Y.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol.

      Volume: 314(2) Issue: 2 Pages: G150-G163

    • DOI

      10.1152/ajpgi.00023.2017

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] S-allyl-glutathione suppresses liver fibrosis by inhibition of excess skewing polarization of macrophages in rats2018

    • Author(s)
      Yukiko Minamiyama1, Shigekazu Takemura2, Hideki Azuma3, Mayuko Osada-Oka1, Michihito Toda2, Keiko Kobayashi1, Hikaru Miyamoto2, Hiroshi ichikawa4 and Shoji Kubo
    • Organizer
      SFRR International 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The suppressive effect of lung fibrosis and polarization to M2-macrophage by liposome chlordronate combined with pirfenidone2018

    • Author(s)
      Michihito Toda, Shinjiro Mizuguchi, Yukiko Minamiyama, Shigekazu Takemura, Hiroko Oka-Yamamoto, Takanori Aota, Hikaru Miyamoto, Noritoshi Nishiyama
    • Organizer
      SFRR International 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of Pirfenidone on rat alveolar macrophage skewing and macrophage-fibroblast interaction.2018

    • Author(s)
      Hikaru Miyamoto, Shinjiro Mizuguchi, Yukiko Minamiyama, Shigekazu Takemura, Hiroko Oka-Yamamoto, Michihito Toda, Takanori Aota, Noritoshi Nishiyama
    • Organizer
      SFRR International 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] S-allyl-glutathione suppresses liver fibrosis by inhibition of excess skewing polarization of macrophages in rats2018

    • Author(s)
      Yukiko Minamiyama, Shigekazu Takemura, Hideki Azuma, Mayuko Osada-Oka, Michitaka Toda, Keiko Kobayashi, Hikaru Miyamoto, Hiroshi ichikawa and Shoji Kubo
    • Organizer
      19th SFRRI Biennial Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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