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

Development of serum biomarkers and therapeutic strategy for non-alcoholic steatohepatitis using liver-specific apoptosis-prone mice

Research Project

Project/Area Number 17K08994
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionToho University

Principal Investigator

TSUCHIYA Yuichi  東邦大学, 医学部, 講師 (10307738)

Co-Investigator(Kenkyū-buntansha) 山崎 創  東邦大学, 医学部, 准教授 (70315084)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords非アルコール性脂肪性肝炎 / アポトーシス / 増殖因子 / 肝再生 / 血清バイオマーカー / cFLIP / 肝前駆細胞
Outline of Final Research Achievements

Non-alcoholic steatohepatitis (NASH) progresses to liver cirrhosis and hepatocellular carcinoma, but specific treatment has not been established. Highly invasive liver biopsy is currently required for NASH diagnosis, and less invasive blood test using specific serum biomarkers is awaited. By using pathological NASH model in gene-manipulated mice, we identified that one growth factor, FGF18, was upregulated upon hepatocyte death and induced the proliferation of hepatocytes in NASH liver. Moreover, we also found that serum FGF18 was increased in human NASH patients, suggesting that FGF18 can be used as a new serum biomarker for NASH diagnosis.

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪性肝疾患(NAFLD)は、飲酒量が少ないにも関わらず肝臓に脂肪が蓄積する疾患である。患者の一部はNASHに進行するが、発症メカニズムは不明な点が多く、有効な治療法も確立していない。またNASHの確定診断に用いられる肝生検は侵襲性が高いことから、血液を用いた侵襲性の低い診断方法の開発が求められている。本研究成果は血液を用いた新たなNASH診断法の開発に貢献するとともに、発症メカニズムの理解と治療法の開発につながる。

Report

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

    (25 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Necroptosis of intestinal epithelial cells induces type 3 innate lymphoid cell-dependent lethal ileitis.2019

    • Author(s)
      Shindo R, Ohmuraya M, Komazawa-Sakon S, Miyake S, Deguchi Y, Yamazaki S, Nishina T, Yoshimoto T, Kakuta S, Koike M, Uchiyama Y, Konishi H, Kiyama H, Mikami T, Moriwaki K, Araki K, Nakano H.
    • Journal Title

      iScience

      Volume: 15 Pages: 536-551

    • DOI

      10.1016/j.isci.2019.05.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] JunB plays a crucial role in development of regulatory T cells by promoting IL-2 signaling2019

    • Author(s)
      Katagiri Takaharu、Yamazaki Soh、Fukui Yuto、Aoki Kotaro、Yagita Hideo、Nishina Takashi、Mikami Tetuo、Katagiri Sayaka、Shiraishi Ayako、Kimura Soichiro、Tateda Kazuhiro、Sumimoto Hideki、Endo Shogo、Kameda Hideto、Nakano Hiroyasu
    • Journal Title

      Mucosal Immunology

      Volume: 12 Issue: 5 Pages: 1104-1117

    • DOI

      10.1038/s41385-019-0182-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regenerating Islet-Derived Protein (Reg)3β Plays a Crucial Role in Attenuation of Ileitis and Colitis in Mice2019

    • Author(s)
      Shindo Ryodai、Katagiri Takaharu、Komazawa-Sakon Sachiko、Ohmuraya Masaki、Takeda Wakami、Nakagawa Yoshiko、Nakagata Naomi、Sakuma Tetsushi、Yamamoto Takashi、Nishiyama Chiharu、Nishina Takashi、Yamazaki Soh、Kameda Hideto、Nakano Hiroyasu.
    • Journal Title

      Biochem Biophys Rep

      Volume: 7 Pages: 100738-100738

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis2019

    • Author(s)
      Tsurusaki Shinya、Tsuchiya Yuichi、Koumura Tomoko、Nakasone Misaki、Sakamoto Taro、Matsuoka Masaki、Imai Hirotaka、Yuet-Yin Kok Cindy、Okochi Hitoshi、Nakano Hiroyasu、Miyajima Atsushi、Tanaka Minoru
    • Journal Title

      Cell Death & Disease

      Volume: 10 Issue: 6 Pages: 449-449

    • DOI

      10.1038/s41419-019-1678-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of novel methods that monitor necroptosis and the release of DAMPs at the single cell resolution2019

    • Author(s)
      Nakano Hiroyasu、Murai Shin、Yamaguchi Yoshifumi、Shirasaki Yoshitaka、Nakabayashi Osamu、Yamazaki Soh
    • Journal Title

      Cell Stress

      Volume: 3 Issue: 2 Pages: 66-69

    • DOI

      10.15698/cst2019.02.177

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers2018

    • Author(s)
      Kurosawa Takeyuki、Miyoshi Shion、Yamazaki Soh、Nishina Takashi、Mikami Tetuo、Oikawa Akira、Homma Sakae、Nakano Hiroyasu
    • Journal Title

      Genes to Cells

      Volume: 24 Issue: 2 Pages: 112-125

    • DOI

      10.1111/gtc.12659

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blockade of TNF receptor superfamily 1 (TNFR1)-dependent and TNFR1-independent cell death is crucial for normal epidermal differentiation2018

    • Author(s)
      Piao Xuehua、Miura Ryosuke、Miyake Sanae、Komazawa-Sakon Sachiko、Koike Masato、Shindo Ryodai、Takeda Junji、Hasegawa Akito、Abe Riichiro、Nishiyama Chiharu、Mikami Tetsuo、Yagita Hideo、Uchiyama Yasuo、Nakano Hiroyasu
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: - Issue: 1 Pages: 213-228.e10

    • DOI

      10.1016/j.jaci.2018.02.043

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The AP-1 transcription factor JunB is required for Th17 cell differentiation2017

    • Author(s)
      Yamazaki Soh、Tanaka Yoshihiko、Araki Hiromitsu、Kohda Akira、Sanematsu Fumiyuki、Arasaki Tomoko、Duan Xuefeng、Miura Fumihito、Katagiri Takaharu、Shindo Ryodai、Nakano Hiroyasu、Ito Takashi、Fukui Yoshinori、Endo Shogo、Sumimoto Hideki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 17402-17402

    • DOI

      10.1038/s41598-017-17597-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Fibroblast growth factor (FGF)18 is a biomarker of non-alcoholic steatotic hepatitis2020

    • Author(s)
      Yuichi Tsuchiya, Kenta Kobayashi, Shinya Tsurusaki, Sachiko Komazawa-Sakon, Minoru Tanaka, Hiroyasu Nakano.
    • Organizer
      AMED-CREST/PRIME Joint International Symposium
    • Related Report
      2019 Annual Research Report
  • [Presentation] cFLIP prevents exacerbation of non-alcoholic steatotic hepatitis by inhibiting apoptosis of hepatocytes2019

    • Author(s)
      Tsuchiya Y, Komazawa-Sakon S, Oikawa A, Mikami T, Nagai H, Tanaka M, Nakano H
    • Organizer
      17th TNF Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] フェロトーシスによる肝細胞死が非アルコール性脂肪性肝炎の初期炎症の起点として重要である2019

    • Author(s)
      鶴崎慎也, 土屋勇一, 今井浩孝, 大河内仁志, 中野裕康, 田中稔
    • Organizer
      第28回日本Cell Death学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] cFLIPは肝細胞において非アルコール性脂肪性肝炎の増悪を防ぐ2019

    • Author(s)
      土屋勇一, 鶴崎慎也, 永井英成, 及川彰, 三上哲夫, 田中稔, 中野裕康
    • Organizer
      第28回日本Cell Death学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝細胞死亢進マウスを用いた非アルコール性脂肪性肝炎のバイオマーカーと治療法の開発2019

    • Author(s)
      土屋勇一
    • Organizer
      Expert seminar of immunology (Vol.8)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] FGF18は非アルコール性脂肪性肝炎において傷害を受けた肝細胞が産生する「ダイイングコード」である2019

    • Author(s)
      土屋勇一, 鶴崎慎也, 永井英成, 及川彰, 三上哲夫, 田中稔, 中野裕康
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] フェロトーシスによる肝細胞死が非アルコール性脂肪性肝炎の初期炎症の起点として重要である2019

    • Author(s)
      鶴崎慎也, 土屋勇一, 今井浩孝, 大河内仁志, 中野裕康, 田中稔
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 転写因子JunBはIL-2シグナルを介して制御性T細胞の分化を調節する2019

    • Author(s)
      片桐翔治, 山崎創, 三上哲夫, 遠藤昌吾, 住本英樹, 亀田秀人, 中野裕康
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腸管上皮バリアにおける転写因子JunBの役割2018

    • Author(s)
      片桐 翔治, 山崎 創, 三上 哲夫, 遠藤 昌吾, 住本 英樹, 亀田 秀人, 中野 裕康
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新規ニューモシスチス肺炎モデルマウスの確立と発症に寄与する免疫不全機構の解明2018

    • Author(s)
      三好 嗣臣, 黒澤 武介, 進藤 綾大, 一色 琢磨, 仁科 隆史, 中林 修, 三宅 早苗, 山崎 創, 本間 栄, 中野 裕康
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] A crucial role of JunB in attenuating epithelial damage-induced colitis through induction of regulatory T cells.2018

    • Author(s)
      Soh Yamazaki, Takeharu Katagiri, Hideki Sumimoto, Hiroyasu Nakano
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] The AP-1 transcription factor JunB is essential for development of Th17 cells2017

    • Author(s)
      Soh Yamazaki, Yoshihiko Tanaka, Yoshinori Fukui, Hideki Sumimoto
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] RORgt-positive cells mediate RIPK3-and MLKL-dependent lethal ileitis in neonatal mice2017

    • Author(s)
      Ryodai Shindo, Soh Yamazaki, Hiroyasu Nakano
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝特異的cFLIP低発現マウスを用いた肝障害モデルの解析2017

    • Author(s)
      山﨑 創, 朴 雪花, 駒澤-左近 幸子, 三宅 早苗, 中林 修, 田中 稔, 大村谷 昌樹, 及川 彰, 角田 宗一郎, 内山 安男, 田中 正人, 中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] RORgt陽性細胞はRIPK3およびMLKL依存性に小腸炎を誘導する2017

    • Author(s)
      進藤 綾大, 大村谷 昌樹, 駒澤 幸子, 三宅 早苗, 山﨑 創, 仁科 隆史, 小西 博之, 木山 博資, 三上 哲夫, 荒木 喜美, 中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] II型肺胞上皮細胞の障害と再生に関する解析2017

    • Author(s)
      三好 嗣臣, 黒澤 武介, 仁科 隆史, 山﨑 創, 本間 栄, 中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 非アルコール性脂肪性肝炎(NASH)の検出方法2018

    • Inventor(s)
      土屋 勇一, 中野, 裕康, 五十嵐 良典, 永井 英成
    • Industrial Property Rights Holder
      東邦大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-245036
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi