• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Novel Liver Cirrhosis Treatment by Drug Repositioning and Leaky Gut Control

Research Project

Project/Area Number 21K08013
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionNara Medical University

Principal Investigator

Yoshiji Hitoshi  奈良県立医科大学, 医学部, 教授 (40336855)

Co-Investigator(Kenkyū-buntansha) 浪崎 正  奈良県立医科大学, 医学部, 講師 (20526850)
鍛治 孝祐  奈良県立医科大学, 医学部, 講師 (20623490)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肝線維化 / ヒアルロン酸ミセル / Leaky Gut / エンドトキシン / ARB / 肝星細胞 / Gut-Liver axis / 肝臓学
Outline of Research at the Start

本研究では大きく2つのアプローチをそれぞれ並行して研究を進めつつ、最終的には両アプローチを合体させて、最も有効で効率的な肝線維化進展抑制を含めた肝硬変病態改善のための治療開発を目指す。即ち、Enhanced Drug-Repositioningとしてヒアルロン酸ミセルを用いた選択的デリバリーシステムを開発し、治療効果を高めて早期に臨床に還元し得る新規治療法の開発を目指す。と共に、Leaky gut に対する Dual cascade blockとしてEXの門脈への流入を抑制すると共に、肝に流入したEX 活性化シグナルを阻害することにより肝硬変の病態進行を抑制する。

Outline of Final Research Achievements

In the development of the Enhanced Drug-Repositioning Delivery System, HA-coated micelles were found to be a promising candidate as a drug delivery vehicle in liver fibrosis, indicating the potential for clinical application. In the development of the Enhanced Drug-Repositioning Delivery System, HA-coated micelles were found to be a promising candidate as a drug delivery vehicle in liver fibrosis, indicating their potential for clinical application. Furthermore, we demonstrated that the control of leaky gut contributes to the improvement of liver pathology, including liver fibrosis, by using a drug that is already in clinical use as a dual cascade blocker of leaky gut.

Academic Significance and Societal Importance of the Research Achievements

本研究からHAコーティングミセルは、肝線維症におけるドラッグデリバリービークルとして有望な候補であることが明らかとなり臨床応用の可能性が示された。さらに、Leaky gut の Dual cascade blockとして肝に流入した内因性エンドトキシン活性化シグナルを阻害することにより肝硬変の病態進行を抑制するために既に臨床で使用されている薬剤賀有効であることを見いだした。これらの成果により臨床応用を見据えたDrug Repositioningによる新規治療法基礎的データが得られた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (21 results)

All 2024 2023 2022 2021

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Tofogliflozin Delays Portal Hypertension and Hepatic Fibrosis by Inhibiting Sinusoidal Capillarization in Cirrhotic Rats2024

    • Author(s)
      Asada Shohei、Kaji Kosuke、Nishimura Norihisa、Koizumi Aritoshi、Matsuda Takuya、Tanaka Misako、Yorioka Nobuyuki、Sato Shinya、Kitagawa Koh、Namisaki Tadashi、Akahane Takemi、Yoshiji Hitoshi
    • Journal Title

      Cells

      Volume: 13 Issue: 6 Pages: 538-538

    • DOI

      10.3390/cells13060538

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blockade of angiotensin II modulates insulin-like growth factor 1-mediated skeletal muscle homeostasis in experimental steatohepatitis2024

    • Author(s)
      Tanaka Misako、Kaji Kosuke、Nishimura Norihisa、Asada Shohei、Koizumi Aritoshi、Matsuda Takuya、Yorioka Nobuyuki、Tsuji Yuki、Fujinaga Yukihisa、Sato Shinya、Namisaki Tadashi、Akahane Takemi、Yoshiji Hitoshi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1871 Issue: 2 Pages: 119649-119649

    • DOI

      10.1016/j.bbamcr.2023.119649

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Combination of an Angiotensin II Receptor and a Neprilysin Inhibitor Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation2023

    • Author(s)
      Suzuki Junya、Kaji Kosuke、Nishimura Norihisa、Kubo Takahiro、Tomooka Fumimasa、Shibamoto Akihiko、Iwai Satoshi、Tsuji Yuki、Fujinaga Yukihisa、Kitagawa Koh、Namisaki Tadashi、Akahane Takemi、Yoshiji Hitoshi
    • Journal Title

      Biomedicines

      Volume: 11 Issue: 5 Pages: 1295-1295

    • DOI

      10.3390/biomedicines11051295

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet-induced rat steatohepatitis.2022

    • Author(s)
      Enomoto M, Kaji K, Nishimura N, Fujimoto Y, Murata K, Takeda S, Tsuji Y, Fujinaga Y, Takaya H, Kawaratani H, Namisaki T, Akahane T, Yoshiji H.
    • Journal Title

      Dig Liver Dis

      Volume: 54 Issue: 10 Pages: 1392-1402

    • DOI

      10.1016/j.dld.2022.04.012

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rifaximin enhances the L carnitine mediated preventive effects on skeletal muscle atrophy in cirrhotic rats by modulating the gut liver muscle axis.2022

    • Author(s)
      Murata K, Kaji K, Nishimura N, Enomoto M, Fujimoto Y, Takeda S, Tsuji Y, Fujinaga Y, Takaya H, Kawaratani H, Namisaki T, Akahane T, Yoshiji H
    • Journal Title

      Int J Mol Med.

      Volume: 50 Issue: 2 Pages: 101-101

    • DOI

      10.3892/ijmm.2022.5157

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of combined farnesoid X receptor agonist and angiotensin II type 1 receptor blocker on ongoing hepatic fibrosis.2022

    • Author(s)
      Namisaki T, Kaji K, Shimozato N, Kaya D, Ozutsumi T, Tsuji Y, Fujinaga Y, Kitagawa K, Furukawa M, Sato S, Sawada Y, Nishimura N, Takaya H, Okura Y, Seki K, Kawaratani H, Moriya K, Noguchi R, Asada K, Akahane T, Mitoro A, Yoshiji H
    • Journal Title

      Indian J Gastroenterol.

      Volume: 41 Issue: 2 Pages: 169-180

    • DOI

      10.1007/s12664-021-01220-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Leaky Gut and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Lenvatinib.2022

    • Author(s)
      Fujimoto Y, Namisaki T, Takeda S, Murata K, Enomoto M, Takaya H, Tsuji Y, Fujinaga Y, Sawada Y, Nishimura N, Kitagawa K, Kaji K, Inoue T, Kawaratani H, Moriya K, Akahane T, Mitoro A, Yoshiji H.
    • Journal Title

      Anticancer Res

      Volume: 42 Issue: 10 Pages: 4895-4905

    • DOI

      10.21873/anticanres.15995

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dual therapy with zinc acetate and rifaximin prevents from ethanol-induced liver fibrosis by maintaining intestinal barrier integrity2021

    • Author(s)
      Fujimoto Y, Kaji K, Nishimura N, Enomoto M, Murata K, Takeda S, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Yoshiji H.
    • Journal Title

      World J Gastroenterol.

      Volume: 28 Issue: 48 Pages: 8323-8342

    • DOI

      10.3748/wjg.v27.i48.8323

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway2021

    • Author(s)
      Ishida K, Kaji K, Sato S, Ogawa H, Takagi H, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Yoshiji H
    • Journal Title

      J Nutr Biochem

      Volume: 89 Pages: 108573-108573

    • DOI

      10.1016/j.jnutbio.2020.108573

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Angiotensin Receptor Blockers Potentiate the Protective Effect of Branched-Chain Amino Acids on Skeletal Muscle Atrophy in Cirrhotic Rats2021

    • Author(s)
      Takeda S, Kaji K, Nishimura N, Enomoto M, Fujimoto Y, Murata K, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Yoshiji H
    • Journal Title

      Mol Nutr Food Res

      Volume: 65 Issue: 24

    • DOI

      10.1002/mnfr.202100526

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Vitamin D Deficiency Exacerbates Alcohol-related Liver Injury via Gut Barrier Disruptionand Hepatic Overload of Endotoxin2023

    • Author(s)
      Shibamoto A, Kaji K, Yoshiji H
    • Organizer
      APASL
    • Related Report
      2023 Annual Research Report
  • [Presentation] Glucagon-like Peptide-1 Receptor Agonist, Semaglutide Attenuates Chronic Liver Disease-induced Skeletal Muscle Atrophy in Diabetic Mice2023

    • Author(s)
      Iwai S, Kaji K, Nishimura N, Kubo T, Tomooka F, Shibamoto A, Suzuki J, Tsuji Y, Fujinaga Y, Kitagawa K, Namisaki T, Akahane T, Yoshiji H
    • Organizer
      APASL
    • Related Report
      2023 Annual Research Report
  • [Presentation] Dual Angiotensin II Receptor and Neprilysin Inhibitor Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation2023

    • Author(s)
      Suzuki J, Kaji K, Nishimura N, Kubo T, Tomooka F, Shibamoto A, Iwai S, Tsuji Y, Fujinaga Y, Kitagawa K, Namisaki T, Akahane T, Yoshiji H
    • Organizer
      APASL
    • Related Report
      2023 Annual Research Report
  • [Presentation] アルコール肝障害モデルマウスを用いた酢酸亜鉛とリファキシミン併用療法による肝繊維化予防効果の検討2022

    • Author(s)
      藤本優樹、鍛治孝祐、、吉治仁志
    • Organizer
      日本消化器病学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肝硬変ラット骨格筋委縮に対するRifaximin/L/carnitine 併用療法の効果2022

    • Author(s)
      村田晃児、鍛治孝祐、吉治仁志
    • Organizer
      日本肝臓学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] アルコール性肝障害モデルマウスを用いた、酢酸亜鉛とリファキシミン併用療法による肝繊維化予防効果の検討2022

    • Author(s)
      藤本優樹、鍛治孝祐、吉治仁志
    • Organizer
      日本肝臓学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Rifaximin および L-carnitine併用による肝硬変ラット骨格筋委縮に対する予防効果の検討2022

    • Author(s)
      村田晃児、鍛治孝祐、吉治仁志
    • Organizer
      日本門脈圧亢進症学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] ARB potentiate the Protective Effect of BCAA on Skeletal Muscle Atrophy in Cirrhotic Rats2022

    • Author(s)
      Takeda S, Kaji K, Yoshiji H
    • Organizer
      日本肝臓学会大会 JDDW2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Rifaximin/L-carnitine 併用による肝硬変ラット骨格筋委縮に対する予防効果2022

    • Author(s)
      村田晃児、鍛治孝祐、高谷広章、瓦谷英人、守屋圭、浪崎正、赤羽たけみ、美登路昭、吉治仁志
    • Organizer
      日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] LPSにより肝星細胞から産生される epiregulin の肝癌進展における役割とその作用機序2022

    • Author(s)
      久保貴裕、鍛治孝祐、吉治仁志
    • Organizer
      日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Lubiprosone と Rifaximin 併用による gut-liver axis 制御とNASH肝繊維化抑制効果2022

    • Author(s)
      榎本壮秀、鍛治孝祐、吉治仁志
    • Organizer
      日本肝臓学会総会
    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi