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The functions of a new WD-repeat domain containing protein naofen to modulate LPS-induced liver dysfunction

Research Project

Project/Area Number 23592689
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionAichi Medical University

Principal Investigator

FENG Guo-Gang  愛知医科大学, 医学部, 講師 (70351111)

Co-Investigator(Kenkyū-buntansha) HONDA Takashi  名古屋大学, 医学(系)研究科(研究院), 特任助教 (10378052)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywordsエンドトキシン(LPS) / クッパー細胞ptosis / TNFα / caspase-3 / アポトーシス / Bcl-2 / Bcl-xL / cytochrome c / LPS / クッパー細胞、 / bupivacaine / NF-κB / エンドトキシン / クッパー細胞 / プロポフォール / WD-repeat protein / チトクロムc
Research Abstract

Endothxin (LPS) causes hepatocytic apoptosis and liver dysfunction, as described in cases of sepsis. In this study, we therefore investigated the functions of a new WD-repeat domain containing protein naofen (WDR35) in LPS-induced liver dysfunction. LPS activated Kuppfer cells and released cytokines, such as TNF-alpha. Which then increased mRNA and protein expression of naofen in hepatocytes. Naofen/WDR35 inhibited expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL, and stimulated apoptosis of hepatocytes. These results suggested that naofen may be involved in endotoxin-induced liver injury, and as a new therapeutic targets for endotoxin-induced liver injury therapy.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (38 results)

All 2014 2013 2012 2011 2010

All Journal Article (20 results) (of which Peer Reviewed: 20 results) Presentation (18 results)

  • [Journal Article] Naofen promotes TNF-α-mediated apoptosis of hepatocytes by activating caspase-3 in lipopolysaccharide-treated rats.2014

    • Author(s)
      Fan JH, Feng GG, Huang L, Tang GD, Jiang HX, Xu J.
    • Journal Title

      World J Gastroenterol.

      Volume: 20(17) Issue: 17 Pages: 4963-4971

    • DOI

      10.3748/wjg.v20.i17.4963

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced Expression of WD repeat -Containing Protein 35 via CaMKK/AMPK Activation in Bupivacaine- Treated Neuro2a Cells2014

    • Author(s)
      Huang L, Kondo F, Gosho M, Feng GG, et al
    • Journal Title

      PLoS One

      Volume: 9 Issue: 5 Pages: e98185-e98185

    • DOI

      10.1371/journal.pone.0098185

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced expression of WD repeat-containing protein 35 via nuclear factor-kappa B activation in bupivacaine-treated Neuro2a cells.2014

    • Author(s)
      Huang L, Kondo F, Harato M, Feng GG, Ishikawa N, Fujiwara Y, Okada S.
    • Journal Title

      PLoS One

      Volume: 9(1) Issue: 1 Pages: e86336-e86336

    • DOI

      10.1371/journal.pone.0086336

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Progressive fibrosis significantly correlates with hepatocellular carcinoma in patients with a sustained virological response.2014

    • Author(s)
      1. Tachi Y, Hirai T, Miyata A, Ohara K, Iida T, Ishizu Y, Kuzuya T, Honda T
    • Journal Title

      Hepatol Res.

      Volume: 印刷中 Issue: 2 Pages: 238-246

    • DOI

      10.1111/hepr.12331

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An increase in lesion density can predict lower local recurrence after transarterial chemoembolization in patients with hepatocellular carcinoma2013

    • Author(s)
      Imai N, Katano Y, Kuzuya T, Honda T, Hayashi K, Ishigami M, et al
    • Journal Title

      Hepatogastroenterology

      Volume: 60 Pages: 965-70

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of the efficacy of ribavirin plus peginterferon alfa-2b for chronic hepatitis C infection in patients with and without coagulation disorders.2013

    • Author(s)
      Honda T, Katano Y, Kuzuya T, Hayashi K, Ishigami M, Itoh A, Hirooka Y, Nakano I, Ishikawa T, Toyoda H, Kumada T, Yamamoto K, Matsushita T, Kojima T, Takamatsu J, Goto H
    • Journal Title

      J Med Virol.

      Volume: 85(2) Issue: 2 Pages: 228-234

    • DOI

      10.1002/jmv.23444

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pegylated interferon monotherapy in patients with chronic hepatitis C with low viremia and its relationship to mutations in the NS5A region and the single nucleotide polymorphism of interleukin-28B.2013

    • Author(s)
      Hayashi K, Katano Y, Masuda H, Ishizu I, Kuzuya T, Honda T, Ishigami M, Itoh A, Hirooka Y, Nakano I, Ishikawa T, Urano F, Yoshioka K, Toyoda H, Kumada T, Goto H.
    • Journal Title

      Hepatol Res

      Volume: 43 Issue: 6 Pages: 580-588

    • DOI

      10.1111/hepr.12005

    • NAID

      10031194559

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced expression of WD repeat-containing protein 35 (WDR35) stimulated by domoic acid in rat hippocampus: involvement of reactive oxygen species generation and p38 mitogen-activated protein kinase activation.2013

    • Author(s)
      Tsunekawa K, Kondo F, Okada T, Feng GG, Huang L, Ishikawa N, Okada S.
    • Journal Title

      BMC Neurosci.

      Volume: - Issue: 1 Pages: 4-4

    • DOI

      10.1186/1471-2202-14-4

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells.2013

    • Author(s)
      Harato M, Huang L, Kondo F, Tsunekawa K, Feng GG, Fan JH, Ishikawa N, Fujiwara Y, Okada S.
    • Journal Title

      BMC Neurosci.

      Volume: - Issue: 1 Pages: 149-149

    • DOI

      10.1186/1471-2202-13-149

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] An increase in lesion density can predict lower local recurrence after transarterial chemoembolization in patients with hepatocellular carcinoma.2013

    • Author(s)
      2. Imai N, Katano Y, Kuzuya T, Honda T, Hayashi K, Ishigami M,
    • Journal Title

      Hepatogastroenterology

      Volume: 60(125) Pages: 965-970

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of naofen in apoptosis of hepatocytes induced by lipopolysaccharide throughmitochondrial signaling in rats2012

    • Author(s)
      Fan JH, Feng GG, Huang L, Tsunekawa K, Honda T,et al
    • Journal Title

      Hepatol Res

      Volume: 42 Pages: 696-705

    • NAID

      10031144286

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b.2012

    • Author(s)
      Toyoda H, Kumada T, Tada T, Hayashi K, Honda T, Katano Y, Goto H, Kawaguchi T, Murakami Y, Matsuda F.
    • Journal Title

      J Med Virol.

      Volume: 84 Issue: 1 Pages: 61-70

    • DOI

      10.1002/jmv.22272

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C.2012

    • Author(s)
      Ishizu Y, Katano Y, Honda T, Hayashi K, Ishigami M, Itoh A, Hirooka Y, Nakano I, Goto H.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 27 Issue: 6 Pages: 1112-6

    • DOI

      10.1111/j.1440-1746.2011.06976.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prevalence of hepatitis C virus genotype 1a in Japan and correlation of mutations in the NS5A region and single-nucleotide polymorphism of interleukin-28B with the response to combination therapy with pegylated-interferon-alpha 2b and ribavirin.2012

    • Author(s)
      Hayashi K, Katano Y, Kuzuya T, Tachi Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Ishikawa T, Nakano I, Urano F, Yoshioka K, Toyoda H, Kumada T, Goto H.
    • Journal Title

      J Med Virol.

      Volume: 84 Issue: 3 Pages: 438-44

    • DOI

      10.1002/jmv.23207

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of naofen in apoptosis of hepatocytes induced by lipopolysaccharide through mitochondrial signaling in rats.2012

    • Author(s)
      Fan JH, Feng GG, Huang L, Tsunekawa K, Honda T, Katano Y, Hirooka Y, Goto H, Kandatsu N, Ando K, Fujiwara Y, Koide T, Okada S, Ishikawa N.
    • Journal Title

      Hepatol Res.

      Volume: 42 Issue: 7 Pages: 696-705

    • DOI

      10.1111/j.1872-034x.2012.00972.x

    • NAID

      10031144286

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A role of naofen in apoptosis of hepatocytes induced by lipopolysaccharide through mitochondrial signaling in rats2012

    • Author(s)
      Jun-Hua Fan, Guo-Gang Feng, Lei Huang, Koji Tsunekawa, Takashi Honda
    • Journal Title

      Hepatology Research

      Volume: 印刷中

    • NAID

      10031144286

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b2012

    • Author(s)
      Toyoda H, Kumada T, Tada T, Hayashi K, Honda T
    • Journal Title

      J Med Virol.

      Volume: 84 Pages: 61-70

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Naofen on Enzyme Activities of Serine Proteases and Matrix Metallo-proteinases2011

    • Author(s)
      Orapin Wongsawatkul, Guo-Gang Feng, et al
    • Journal Title

      International Journal of Pharmacology

      Volume: 7 Issue: 3 Pages: 388-393

    • DOI

      10.3923/ijp.2011.388.393

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy2011

    • Author(s)
      Hayashi K, Katano Y, Honda T, et al
    • Journal Title

      Liver Int

      Volume: 31(9) Pages: 1359-65

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy2011

    • Author(s)
      Hayashi K, Katano Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Ishikawa T
    • Journal Title

      Liver Int.

      Volume: 31 Pages: 1359-1365

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] NF-κBはWDR35の発現に関与する2014

    • Author(s)
      馮国剛、黄磊、石川直久
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] AMPKはbupivacine処理Neuro2a細胞におけるWDR35の発現に関与する2014

    • Author(s)
      2.黄磊、近藤文雄、馮国剛、藤澤明子。AMPKはbupivacine処理Neuro2a細胞におけるWDR35の発現に関与する。第87回日本薬理学会年会。2014.3.19-21.仙台
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] NF-κBはWDR35の発現に関与する2014

    • Author(s)
      馮 国剛、黄 磊、石川 直久、近藤 文雄、岡田 尚志郎
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] LPSを投与したラット肝細胞のアポトーシスに対するプロポフォールの保護作用2013

    • Author(s)
      馮国剛、神立伸久
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Bupivacine処理Neuro2a細胞におけるWDR35の発現に対するNF-κBの関与2013

    • Author(s)
      黄磊、近藤文雄、馮国剛、恒川幸司
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Clinical doses of propofol reduce sepsis-induced hepatocyte apoptosis via regulation of TNFαexpression in the rats2013

    • Author(s)
      Hiroyuki Kinoshita, Kazuo Ando, Guo-Gang Feng, et al
    • Organizer
      ANESTHESIOLOGY^TM2013 annual meeting in U.S
    • Place of Presentation
      San Francisco
    • Related Report
      2013 Final Research Report
  • [Presentation] Clinical doses of propofol reduce sepsis-induced hepatocyte apoptosis via regulation of TNFα expression in the rats2013

    • Author(s)
      Hiroyuki Kinoshita, Kazuo Ando, Guo-Gang Feng, Jiazeng Li, Jiazhen Jiang, Takahiko Akahori, Eri Matsunag, Emi Nakamura, Yoshihiro Fujiwara
    • Organizer
      ANESTHESIOLOGY 2013 annual meeting in U.S.
    • Place of Presentation
      San Francisco
    • Related Report
      2013 Annual Research Report
  • [Presentation] Effect of combination therapy peginterferon alfa-2b and ribavirin on prevention of hepatocellular carcinoma in patients with chronic hepatitis C and normal aminotransferase levels2013

    • Author(s)
      1. Takashi Honda, Yoshiaki Katano, Satoshi Nakano, Yoji Ishizu, Teiji Kuzuya, Kazuhiko Hayashi, Masatoshi Ishigami, Hidemi Goto
    • Organizer
      DDW2013 (米国消化器病週間)
    • Place of Presentation
      Orlando
    • Related Report
      2013 Annual Research Report
  • [Presentation] HBe抗体陽性B型慢性肝炎における経過予測に必要なウイルス遺伝子変異の検討2013

    • Author(s)
      本多 隆、片野義明、後藤秀実
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] LPSを投与したラット肝細胞のアポトーシスに対するプロポフォールの保護作用2013

    • Author(s)
      馮 国剛、神立 伸久、黄 磊、近藤 文雄、石川 直久、藤原 祥、岡田 尚志郎
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] ドウモイ酸投与ラットの海馬における新規生体内物質Naofenの役割2012

    • Author(s)
      恒川幸司、近藤文雄、黄磊、馮国剛
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] ブピバカインはNeuro2a細胞におけるnaofen発現を増加させる2012

    • Author(s)
      黄磊、馮国剛、范俊華、恒川幸司
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] A Case of HBeAgSerocoversion with Emerged Mutation of rt M 204 I/V in the Patients with Hepatitis B and HIV2012

    • Author(s)
      Honda T, Katano Y, Kuzuya T, Tachi Y, Hayashi K
    • Organizer
      アジア太平洋肝臓学会議 (APASL)
    • Place of Presentation
      タイペイ
    • Related Report
      2011 Research-status Report
  • [Presentation] 新規生体内物質naofenはミトコンドリア経路を介してLPSにより誘導される肝細胞アポトーシスを促進する2011

    • Author(s)
      馮国剛、范俊華、黄磊、石川直久
    • Organizer
      第20回日本Cell Death学会学術集会
    • Place of Presentation
      東京大学薬学総合研究棟
    • Related Report
      2013 Final Research Report
  • [Presentation] 新規生体内物質naofenはミトコンドリア経路を介してLPSにより誘導される肝細胞アポトーシスを促進する2011

    • Author(s)
      馮 国剛、范 俊華、黄 磊、石川 直久、岡田 尚志郎
    • Organizer
      第20回日本Cell Death学会学術集会
    • Place of Presentation
      東京大学 (薬学総合研究棟)
    • Related Report
      2011 Research-status Report
  • [Presentation] Efficacy of Combination Therapy Peginterferon Alfa-2B and Rebavirin on Prevention of Hepatocellular Carcinoma in order Patients with Chronic Hepatitis C2011

    • Author(s)
      Honda T, Katano Y, Kuzuya T, Tachi Y, Hayashi K
    • Organizer
      米国肝臓学会議 (AASLD)
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2011 Research-status Report
  • [Presentation] HIV、HBV重複感染例でHBVに対するラミブジン耐性株の出現後HBe抗体陽性が持続し肝炎が沈静化した1例2011

    • Author(s)
      本多 隆, 片野 義明, 中野 聡, 増田 寛子, 及部 祐加子
    • Organizer
      第39回日本肝臓学会西部会
    • Place of Presentation
      岡山
    • Related Report
      2011 Research-status Report
  • [Presentation] LPSは肝臓でnaofen発現を増加させてアポトーシスを引き起こす2010

    • Author(s)
      范俊華、馮国剛、恒川幸司、石川直久
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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