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2013 Fiscal Year Final Research Report

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

Research Project

  • PDF
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
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
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.

  • Research Products

    (24 results)

All 2014 2013 2012 2011 2010

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (9 results)

  • [Journal Article] Naofen promotes TNF-α- mediated apoptosis of hepatocytes by activating caspase-3 in lipopolysaccharide -treated rats2014

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

      World J Gastroenterol

      Volume: 20 Pages: 4963-71

    • DOI

      10.3748/wjg.v20.i17.4963

    • 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 Pages: e98185

    • DOI

      10.1371/journal.pone.0098185

    • Peer Reviewed
  • [Journal Article] Enhanced expression of WD repeat-containing protein 35 via nuclear factor-kappa B activation in bupivacaine-treated Neuro2a cells2014

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

      PLoS One

      Volume: 9 Pages: e86336

    • DOI

      10.1371/journal.pone.0086336

    • Peer Reviewed
  • [Journal Article] Progressive fibrosis significantly correlates with hepatocellular carcinoma in patients with a sustained virological response2014

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

      Hepatol Res

    • DOI

      10.1111/hepr.12331

    • 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

    • DOI

      10.5754/hge121229

    • 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 disorders2013

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

      J Med Virol

      Volume: 85(2) Pages: 228-234

    • DOI

      10.1002/jmv.23444

    • 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-28B2013

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

      Hepatol Res

      Volume: 43(6) Pages: 580-8

    • DOI

      10.1111/hepr.12005

    • 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 activation2013

    • Author(s)
      Tsunekawa K, Kondo F, Okada T, Feng GG, et al
    • Journal Title

      BMC Neurosci

      Volume: 14 Pages: 4

    • DOI

      10.1186/1471-2202-14-4

    • 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

    • DOI

      10.1111/j.1872-034X.2012.00972

    • Peer Reviewed
  • [Journal Article] Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells2012

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

      BMC Neurosci

      Volume: 13 Pages: 149

    • DOI

      10.1186/1471-2202-13-149

    • 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, et al
    • Journal Title

      J Med Virol

      Volume: 84 Pages: 61-70

    • DOI

      10.1002/jmv.22272

    • Peer Reviewed
  • [Journal Article] Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C2012

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

      J Gastroenterol Hepatol

      Volume: 27 Pages: 1112-6

    • DOI

      10.1111/j.1440-1746.2011.06976.x

    • 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 ribavirin2012

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

      J Med Virol

      Volume: 84 Pages: 438-44

    • DOI

      10.1002/jmv.23207

    • 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 Pages: 388-393

    • DOI

      10.3923/ijp.2011.388.393

    • 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

    • DOI

      10.1111/j.1478-3231.2011.02571

    • 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
    • Year and Date
      20140319-21
  • [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
    • Year and Date
      20140319-21
  • [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
    • Year and Date
      20131012-16
  • [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
    • Year and Date
      20130321-23
  • [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
    • Year and Date
      20130321-23
  • [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
    • Year and Date
      20120314-16
  • [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
    • Year and Date
      20120314-16
  • [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
    • Year and Date
      20110729-30
  • [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
    • Year and Date
      20100316-18

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Published: 2015-07-16  

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