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Study of the nuclear receptors involved in fatty livers; establishment of a new pathological model and development of therapeutic application.

Research Project

Project/Area Number 22590354
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionGunma University

Principal Investigator

INOUE Yusuke  群馬大学, 大学院・工学研究科, 准教授 (90304302)

Co-Investigator(Kenkyū-buntansha) KUWAHARA Masayasu  群馬大学, 大学院・工学研究科, 准教授 (40334130)
NAMEKI Nobukazu  群馬大学, 大学院・工学研究科, 准教授 (80302959)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脂肪肝 / 核内受容体 / HNF4α / PPARα / モデルマウス / PPAR / 肝臓
Research Abstract

Deletion of haptic PPARα in liver-specific HNF4α-null mice (KO mice) improved fatty livers. To investigate the pathogenic mechanism of fatty livers, DNA binding activity of haptic PPARα was analysed. As a result, DNA binding activity of hepatic PPARα was decreased in KO mice. Expression of hepatic PPARγ1 and PGC1α was also increased and transactivation of hepatic PPARα target genes was observed in KO mice. These results indicate that hepatic PPARγ1, PGC1α, and unidentified ligands for PPARα /γ1 could transactivate the PPARαtarget genes and induce fatty lives in KO mice.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (41 results)

All 2013 2012 2011 2010

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (34 results) Book (1 results)

  • [Journal Article] DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells2013

    • Author(s)
      Yamamoto K, Murata H, Putranto EW, Kataoka K, Motoyama A, Hibino T, Inoue Y, Sakaguchi M, and Huh NH
    • Journal Title

      Oncol Rep

      Volume: 29 Issue: 3 Pages: 1073-1079

    • DOI

      10.3892/or.2012.2191

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Solutionstructure and siRNA-mediated knockdown analysis of the mitochondorial disease-related protein C12orf652012

    • Author(s)
      Kogure H, Hikawa Y, Hagihara M, Tochio N, Koshiba S, Inoue Y, Guntert P, Kigawa, T, Yokoyama S, and Nameki N
    • Journal Title

      Proteins

      Volume: 80 Issue: 11 Pages: 2629-2642

    • DOI

      10.1002/prot.24152

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of mouse coagulation gene transcription following acute in vivo delivery of synthetic small interfering RNAs targeting HNF4α and C/EBP2012

    • Author(s)
      Safdar H, Cheung KL, Vos HL, Gonzalez FJ, Reitsma PH, Inoue Y, and van Vlijmen BJ
    • Journal Title

      PLoS One

      Volume: 7 Issue: 6 Pages: e38104-e38104

    • DOI

      10.1371/journal.pone.0038104

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of modified siRNA bearing C-5 polyamine-substituted pyrimidine nucleoside in their 3'-overhang regions and its RNAi activity2011

    • Author(s)
      Masud MM, Masuda T, Inoue Y, Kuwahara M, Sawai H, and and Ozaki H.
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 21 Issue: 2 Pages: 715-717

    • DOI

      10.1016/j.bmcl.2010.11.125

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of hepatocyte nuclear factor 4α in regulating mouse hepatic anticoagulation and fibrinolysis gene transcript levels2010

    • Author(s)
      Safdar H, Inoue Y, van Puijvelde GH, Reitsma PH, and van Vlijmen BJ
    • Journal Title

      J. Thromb. Haemost

      Volume: 8 Issue: 12 Pages: 2839-2841

    • DOI

      10.1111/j.1538-7836.2010.04080.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Solution structure of the catalytic domain of the mitochondrial protein ICT1 that is essential for cell vitality2010

    • Author(s)
      Handa Y, Hikawa Y, Tochio N, Kogure H, Inoue M, Koshiba M, Guntert P, Inoue Y, Kigawa T, Yokoyama S, and Nameki N
    • Journal Title

      J. Mol. Biol

      Volume: 404 Issue: 2 Pages: 260-273

    • DOI

      10.1016/j.jmb.2010.09.033

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Activation of hepatic PPARaa cascade in liver-specific HNF4α-deficient mice2012

    • Author(s)
      Saito C, Gonzalez FJ, Inoue Y
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      マリンメッセ福岡(福 岡県)
    • Year and Date
      2012-12-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Transcriptional regulation of hepatic transferrin receptor 22012

    • Author(s)
      Matsuo S, Fujimura T, Mizui Y, Gonzalez FJ, Inoue Y.
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      マリンメッ セ福岡(福岡県)
    • Year and Date
      2012-12-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Regulation of transcriptional control ofcomplement C8a gene by HNF4α2012

    • Author(s)
      Yokota S, Sakamoto N, Gonzalez FJ, Inoue Y
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      マリンメッセ福 岡(福岡県)
    • Year and Date
      2012-12-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Analysis of transcriptional regulation of microRNA-194/192 by HNF4α2012

    • Author(s)
      Kannari M, Tsuchida Y, Saito C, Gonzalez FJ, Inoue Y
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      マリンメッセ福岡(福岡県)
    • Year and Date
      2012-12-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Low blood glucose levels in liver-specific HNF4α-null mice by decreased expression of hepatic glucagon receptor2012

    • Author(s)
      Matsuta T, Kannari M, Gonzalez FJ, Inoue Y.
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      マリンメッセ福岡(福岡県)
    • Year and Date
      2012-12-12
    • Related Report
      2012 Final Research Report
  • [Presentation] 2 型トランスフェリン 受容体遺伝子の転写活性化機構の解析2012

    • Author(s)
      松尾峻介、藤村岳史、水井由美子、Frank J. Gonzalez、井上裕介
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      群馬大 学昭和キャンパス(群馬県)
    • Year and Date
      2012-06-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスの血糖値低下とグルカゴン受容体のプロモーター解析2012

    • Author(s)
      松田強志、神成真名、Frank J. Gonzalez、井上裕介
    • Organizer
      平成24年度日本生化学会関東支部例会
    • Place of Presentation
      群馬大学昭和キャンパス(群馬県)
    • Year and Date
      2012-06-23
    • Related Report
      2012 Final Research Report
  • [Presentation] HNF4αによる補体遺伝子 C8γの転 写活性化機構の解析2012

    • Author(s)
      横田聡美、坂本憲明、Frank J. Gonzalez、 井上裕介
    • Organizer
      平成24年度日本生化学会関東支部例会
    • Place of Presentation
      群馬大学昭 和キャンパス(群馬県)
    • Year and Date
      2012-06-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスにおけるPPARαの発現・機能解析2012

    • Author(s)
      齊藤千夏、Frank J.Gonzalez、井上裕介
    • Organizer
      平成24年度日本生化学会関東支部例会
    • Place of Presentation
      群馬大学昭和キャンパス(群馬県)
    • Year and Date
      2012-06-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓 HNF4αによる miR-194/192 の発現制御機構の解析2012

    • Author(s)
      神成真名、土田雄一、齊藤千夏、Frank J. Gonzalez、 井上裕介
    • Organizer
      平成24年度日本生化学会関東支部例会
    • Place of Presentation
      群馬大学昭和キャンパス(群馬県)
    • Year and Date
      2012-06-23
    • Related Report
      2012 Final Research Report
  • [Presentation] ミトコンドリアにおけるICT1による翻訳停滞解消機構の解明2012

    • Author(s)
      小暮裕幸、樋川雄介、萩原護、井上裕介、行木信一
    • Organizer
      平成24年度日本生化学会関東支部例会
    • Place of Presentation
      群馬大学昭和キャンパス(群馬県)
    • Year and Date
      2012-06-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 2 型トランスフェリン受容体遺伝子の転写活性化機構の解析2012

    • Author(s)
      松尾峻介、藤村岳史、水井由美子、Frank J. Gonzalez、井上裕介
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      前橋市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスの血糖値低下とグルカゴン受容体のプロモーター解析2012

    • Author(s)
      松田強志、神成真名、Frank J. Gonzalez、井上裕介
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      前橋市
    • Related Report
      2012 Annual Research Report
  • [Presentation] HNF4αによる補体遺伝子C8γの転写活性化機構の解析2012

    • Author(s)
      横田聡美、坂本憲明、Frank J. Gonzalez、井上裕介
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      前橋市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 齊藤千夏、Frank J. Gonzalez、井上裕介2012

    • Author(s)
      肝臓特異的HNF4α欠損マウスにおけるPPARαの発現・機能解析
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      前橋市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 神成真名、土田雄一、齊藤千夏、Frank J. Gonzalez、井上裕介2012

    • Author(s)
      肝臓HNF4αによるmiR-194/192 の発現制御機構の解析
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      前橋市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Low blood glucose levels in liver-specific HNF4α-null mice by decreased expression of heaptic glucagon receptor2012

    • Author(s)
      Tsuyoshi Matsuta, Mana Kannari, Frank J. Gonzalez, Yusuke Inoue
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of transcriptional regulation of microRNA-194/192 by HNF4α2012

    • Author(s)
      Mana Kannari, Yuichi Tsuchida, Chinatsu Saito, Frank J. Gonzalez, Yusuke Inoue
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Regulation of transcriptional control of complement C8γ gene by HNF4α2012

    • Author(s)
      Satomi Yokota, Noriaki Sakamoto, Frank J. Gonzalez, Yusuke Inoue
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Activation of hepatic PPARα cascade in liver-specific HNF4α-deficient mice2012

    • Author(s)
      Chinatsu Saito, Frank J. Gonzalez, Yusuke Inoue
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Transcriptional regulation of hepatic transferrin receptor 22012

    • Author(s)
      Shunsuke Matsuo, Takafumi Fujimura, Yumiko Mizui, Frank J. Gonzalez, Yusuke Inoue
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Transcriptional analysis of the geneencoding the mitochondrial proteinC12orf62011

    • Author(s)
      樋川雄介、小暮裕幸、井上裕介、行木信一
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2011-12-15
    • Related Report
      2012 Final Research Report
  • [Presentation] Transcriptional Analysis of the Gene Encoding the Mitochondrial Protein ICT12011

    • Author(s)
      Kogure H, Handa Y, Hikawa Y, Inoue Y and Nameki N.
    • Organizer
      The 16th Annual Meeting of the RNA Society and The 13th Annual Meeting of the RNA Society of Japan
    • Place of Presentation
      京都 国際会館(京都府)
    • Year and Date
      2011-06-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Hepatic HNF4α is required for microRNA expression2010

    • Author(s)
      Tsuchida Y, Suzuki J, Nakamura H, Nakamura T, Gonzalez FJ, Inoue Y.
    • Organizer
      第33回日本分子生物学会
    • Place of Presentation
      パ シフィコ横浜(神奈川県)
    • Year and Date
      2010-12-12
    • Related Report
      2012 Final Research Report
  • [Presentation] HNF4αを介した補体成分C8aの発現制御機構の解析2010

    • Author(s)
      横田聡美、坂本憲明、Frank J.Gonzalez、井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓グルカゴン受容体のエピジェネティッ ク制御2010

    • Author(s)
      宮岡広樹、Frank J. Gonzalez、井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域地場産業振興 センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] トランスフェリン受容 体 2 の発現制御機構の解析2010

    • Author(s)
      松尾峻介、藤村岳史、水井由美子、Frank J. Gonzalez、井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐 生地域地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓特異的 HNF4α欠損マウスにおけるプロテ オーム解析2010

    • Author(s)
      中村遥、Frank J. Gonzalez、井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域地場産業 振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓 HNF4αによる miroRNA の発現制御2010

    • Author(s)
      土田雄一、中村遥、中村宜広、Frank J. Gonzalez、井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域 地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスにおけるHNF4aの発現解析2010

    • Author(s)
      鈴木淳子、入江亮太、FrankJ.Gonzalez、井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスにお ける HNF4aの発現解析2010

    • Author(s)
      鈴木淳子、入江亮太、Frank J. Gonzalez、 井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地 域地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスにおけるHNF4a の発現解析2010

    • Author(s)
      鈴木淳子、入江亮太、Frank J. Gonzalez、井上裕介
    • Organizer
      群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスにおけるプロテオーム解析2010

    • Author(s)
      井上裕介
    • Organizer
      第5回群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝臓特異的HNF4α欠損マウスにおけるHNF4γの発現解析2010

    • Author(s)
      井上裕介
    • Organizer
      第5回群馬大学ファイブロバイオプロセス研究会
    • Place of Presentation
      桐生地域地場産業振興センター(群馬県)
    • Year and Date
      2010-11-24
    • Related Report
      2010 Annual Research Report
  • [Book] ヒトにおける食物の消化・吸収・代謝と異物の代謝. 石原勝敏, 末光隆志 (総編集)、生物の事典2010

    • Author(s)
      井上裕介
    • Publisher
      朝倉書店
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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