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The role of hepatocyte Grb2-associated binder 1 in impaired liver regeneration of NALFD

Research Project

Project/Area Number 16K19341
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

FURUTA KUNIMARO  大阪大学, 医学部附属病院, 特任助教(常勤) (50773834)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsGab1 / NAFLD / 肝再生 / 細胞死 / Gab1 / Gab2
Outline of Final Research Achievements

Grb2-associated binder 1 (Gab1) plays a crucial role in the live regeneration. Liver regeneration is known to be impaired in non-alcoholic fatty liver disease (NAFLD) patients. However, the role of Gab1 in impaired liver regeneration in NAFLD has remained unclear. To investigate this issue, we examined the liver injury of hepatocyte specific Gab1 conditional knockout (KO) mice of in murine NAFLD models. Wild type (WT) and KO mice were fed with high-fat and high-cholesterol (HFHC) diet or methionine- and choline-deficient (MCD) diet for 8 weeks. In a HFHC diet model, KO mice showed a significant increase in body weight and hepatic cholesterol content compared with WT mice, however, did not show any difference in serum ALT levels. In contrast, in a MCD diet model, KO mice showed a significant increase in serum ALT levels compared with WT mice. The data indicate the possible role of Gab1 in hepatic lipid metabolism and hepatocyte injury in NAFLD.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Increased expression of Forkhead box M1 transcription factor is associated with clinicopathological features and confers a poor prognosis in human hepatocellular carcinoma.2017

    • Author(s)
      Egawa M, Yoshida Y, Ogura S, Kurahashi T, Kizu T, Furuta K, Kamada Y, Chatani N, Hamano M, Kiso S, Hikita H, Tatsumi T, Eguchi H, Nagano H, Doki Y, Mori M, Takehara T
    • Journal Title

      Hepatol Res.

      Volume: 印刷中 Issue: 11 Pages: 1196-1205

    • DOI

      10.1111/hepr.12854

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Frequency of, and factors associated with, hepatitis B virus reactivation in hepatitis C patients treated with all-oral direct-acting antivirals: Analysis of a Japanese prospective cohort2017

    • Author(s)
      Doi Akira、Sakamori Ryotaro、Tahata Yuki、Urabe Ayako、Morishita Naoki、Yamada Ryoko、Furuta Kunimaro、Kodama Takahiro、Hikita Hayato、Yakushijin Takayuki、Ohkawa Kazuyoshi、Kaneko Akira、Imai Yasuharu、Tatsumi Tomohide、Takehara Tetsuo
    • Journal Title

      Hepatology Research

      Volume: 47 Issue: 13 Pages: 1438-1444

    • DOI

      10.1111/hepr.12919

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gab1 adaptor protein acts as a gatekeeper to balance hepatocyte death and proliferation during acetaminophen-induced liver injury in mice.2016

    • Author(s)
      Furuta K, Yoshida Y, Ogura S, Kurahashi T, Kizu T, Maeda S, Egawa M, Chatani N, Nishida K, Nakaoka Y, Kiso S, Kamada Y, Takehara T.
    • Journal Title

      Hepatology

      Volume: 63 Issue: 4 Pages: 1340-1355

    • DOI

      10.1002/hep.28410

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 慢性肝疾患における新規炎症制御因子としてのFoxM1転写因子の意義2017

    • Author(s)
      倉橋知英、吉田雄一、小倉智志、柄川真弓、古田訓丸、鎌田佳宏、木曽真一、疋田隼人、巽智秀、竹原徹郎
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] NAFLD病態進展における肝細胞FoxM1転写因子の役割2017

    • Author(s)
      倉橋知英、吉田雄一、小倉智志、柄川真弓、古田訓丸、鎌田佳宏、木曽真一、疋田隼人、巽智秀、竹原徹郎
    • Organizer
      第42回日本肝臓学会西部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Lipid metabolism regulates oncogenic FoxM1 transcription factor in human hepatocellular carcinoma via the mevalonate-Rho pathway2017

    • Author(s)
      Yuichi Yoshida, Satoshi Ogura, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Tomohide Tatsumi and Tetsuo Takehara
    • Organizer
      第68回米国肝臓学会議
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Overexpression of FoxM1 transcription factor in murine hepatocytes results in hepatocyte death and liver inflammation2017

    • Author(s)
      Tomohide Kurahashi, Yuichi Yoshida, Satoshi Ogura, Mayumi Egawa, Kunimaro Furuta, Yoshihiro Kamada, Shinichi Kiso, Hayato Hikita, Tomohide Tatsumi, Tetsuo Takehara
    • Organizer
      第68回米国肝臓学会議
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FoxM1転写因子による慢性肝疾患の制御機構:新規マウスモデルを用いた検討2016

    • Author(s)
      倉橋知英、吉田雄一、小倉智志、柄川真弓、古田訓丸、鎌田佳宏、木曽真一、疋田隼人、巽智秀、竹原徹郎
    • Organizer
      第41回日本肝臓学会東部会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-12-08
    • Related Report
      2016 Research-status Report
  • [Presentation] FoxM1転写因子を介した癌脂質代謝プログラムに基づく新たな肝癌治療戦略2016

    • Author(s)
      小倉智志、吉田雄一、倉橋知英、柄川真弓、古田訓丸、木曽真一、鎌田佳宏、疋田隼人、 巽智秀、竹原徹郎
    • Organizer
      第41回日本肝臓学会東部会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-12-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Metabolic regulation of FoxM1 transcription factor by mevalonate-Rho pathways in human hepatocarcinoma.2016

    • Author(s)
      Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Tomohide Tatsumi and Tetsuo Takehara.
    • Organizer
      The Liver Meeting 2016 - AASLD
    • Place of Presentation
      HYNES CONVENTION CENTER, BOSTON, MA, USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hepatic overexpression of oncogenic FoxM1 transcription factor promotes hepatocyte death and hepatic inflammation in mice.2016

    • Author(s)
      Tomohide Kurahashi, Yuichi Yoshida, Satoshi Ogura, Mayumi Egawa, Kunimaro Furuta, Yoshihiro Kamada, Shinichi Kiso, Hayato Hikita, Tomohide Tatsumi, Tetsuo Takehara.
    • Organizer
      The Liver Meeting 2016 - AASLD
    • Place of Presentation
      HYNES CONVENTION CENTER, BOSTON, MA, USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 急性肝不全病態においてGab1 は肝細胞運命の決定を担う2016

    • Author(s)
      古田訓丸, 吉田雄一, 倉橋知英, 小倉智志, 柄川真弓, 木曽真一, 鎌田佳宏, 竹原徹郎
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ幕張(千葉県千葉市美浜区)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] FoxM1 転写因子を介した新たな肝癌脂質代謝制御:治療標的としての可能性について2016

    • Author(s)
      小倉智志、吉田雄一、柄川真弓、倉橋 知英、古田訓丸、木曽真一、鎌田佳宏、竹原徹郎
    • Organizer
      第102回 日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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