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Ductular metaplasia of hepatocytes : its demonstration in vivo and the study of the mechanism

Research Project

Project/Area Number 21590426
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionAsahikawa Medical College

Principal Investigator

NISHIKAWA Yuji  旭川医科大学, 医学部, 教授 (90208166)

Co-Investigator(Kenkyū-buntansha) ENOMOTO Katsuhiko  秋田大学, 医学部, 教授 (20151988)
OMORI Yasufumi  秋田大学, 医学部, 講師 (90323138)
YOSHIOKA Toshiaki  秋田大学, 医学部, 助教 (80302264)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肝細胞 / 胆管上皮細胞 / 慢性肝傷害 / 細胆管反応 / 分化転換 / JNK-c-Jun経路 / 肝幹細胞 / JNL-c-Jun経路 / 肝細胞標識追跡系 / 慢性肝障害 / JNK-c-lun経路
Research Abstract

To demonstrate transdifferentiation of hepatocytes to bile dutular cells in vivo, we established a hepatocyte-lineage tracing system, in which hepatocytes from Alb^<Cre/WT>ROSA26R (β-galactosidase-positive) were transplanted into the livers of C56BL/6J mice. In chronic liver injury induced by CCl_4 or DDC in these mice, we often found β-galactosidase-positive and cytokeratin 19-positive ductules, demonstrating that ductular transdifferentiation actually occurs in vivo. In addition, we found that hepatocyes from MKK7 KO mice (MKK7^<fl/fl>Alb^<Cre/WT>) showed less prominent branching morphogenesis as compared with those from control mice (MKK7^<fl/+>Alb^<Cre/WT>).

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (44 results)

All 2012 2011 2010 2009 Other

All Journal Article (14 results) (of which Peer Reviewed: 6 results) Presentation (29 results) Remarks (1 results)

  • [Journal Article] Transdifferentiation ofmature hepatocytes into bile duct/ductulecells within a collagen gel matrix2012

    • Author(s)
      Nishikawa Y
    • Journal Title

      Methods Mol. Biol

      Volume: 826 Pages: 153-60

    • DOI

      10.1007/978-1-61779-468-1_13

    • ISBN
      9781617794674, 9781617794681
    • Related Report
      2011 Final Research Report
  • [Journal Article] Transdifferentiation of mature hepatocytes into bile duct/ductule cells within a collagen gel matrix2012

    • Author(s)
      Nishikawa Y
    • Journal Title

      Methods Mol.Biol.

      Volume: 826 Pages: 153-160

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 肝臓病理学-細胆管反応をめぐって2011

    • Author(s)
      西川祐司
    • Journal Title

      病理と臨床

      Volume: 29 Pages: 1263-1269

    • Related Report
      2011 Final Research Report
  • [Journal Article] Replacement of liver parenchyma inanalbuminemic rats with allogenichepatocytes is facilitated by intrabonemarrow-bone marrow transplantation2011

    • Author(s)
      Inagaki M, Furukawa H, Satake Y, Okada Y, Chiba S, Nishikawa Y, Ogawa K
    • Journal Title

      CellTransplant

      Volume: 20 Issue: 9 Pages: 1479-891

    • DOI

      10.3727/096368910x547453

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic accumulation ofconnexin32 expands cancer stem cellpopulation in human HuH7 hepatoma cellsby enhancing its self-renewal.2011

    • Author(s)
      Kawasaki Y, Omori Y, Li Q, Nishikawa Y, Yoshioka T, Yoshida M, Ishikawa K, Enomoto K
    • Journal Title

      Int J Cancer

      Volume: 128 Issue: 1 Pages: 51-62

    • DOI

      10.1002/ijc.25308

    • Related Report
      2011 Final Research Report
  • [Journal Article] Replacement of liver parenchyma in analbuminemic rats with allogenic hepatocytes is facilitated by intrabone marrow-bone marrow transplantation2011

    • Author(s)
      Inagaki M, et al.
    • Journal Title

      Cell Transplant.

      Volume: 20 Pages: 1479-1489

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肝臓病理学-細胆管反応をめぐって-2011

    • Author(s)
      西川祐司
    • Journal Title

      病理と臨床

      Volume: 29 Pages: 1263-1269

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Significance of integrin αvβ5and erbB3 in enhanced cell migration andliver metastasis of colon carcinomasstimulated by hepatocyte-derivedheregulin2010

    • Author(s)
      Yoshioka T, Nishikawa Y, Ito R, Kawamata M, Doi Y, YamamotoY, YoshidaM, Omori Y, Kotanagi H, Masuko T, Enomoto K
    • Journal Title

      Cancer Sci

      Volume: 101 Issue: 9 Pages: 2011-2018

    • DOI

      10.1111/j.1349-7006.2010.01640.x

    • Related Report
      2011 Final Research Report
  • [Journal Article] Significance of integrin avβ5 and erbB3 in enhanced cell migration and liver metastasis of colon carcinomas stimulated by hepatocyte-derived heregulin.2010

    • Author(s)
      Yoshioka T, Nishikawa Y, et al.
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 2011-2018

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic accumulation of connexin32 expands cancer stem cell population in human HuH7 hepatoma cells by enhancing its self-renewal.2010

    • Author(s)
      Kawasaki Y, Omori Y, Li Q, Nishikawa Y, Yoshioka T, etc.
    • Journal Title

      International Journal of Cancer (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mast cellleukemia with rapidly progressing portalhypertension2009

    • Author(s)
      Yoshida M, Nishikawa Y, Yamamoto Y, Doi Y, Tokairin T, Yoshioka T, Omori Y, Watanabe A, Takahashi N, Yoshioka T, Miura I, Sawada K, Enomoto K
    • Journal Title

      Pathol Int

      Volume: 59 Issue: 11 Pages: 817-822

    • DOI

      10.1111/j.1440-1827.2009.02451.x

    • NAID

      10027382281

    • Related Report
      2011 Final Research Report
  • [Journal Article] Suppressive effect of orthovanadate onhepatic stellate cell activation and liverfibrosis in rats2009

    • Author(s)
      Nishikawa Y, Ohi N, Yagisawa A, Doi Y, Yamamoto Y, Yoshida M, Tokairin T, Yoshioka T, Omori Y, Enomoto K
    • Journal Title

      Am J Pathol

      Volume: 174 Issue: 3 Pages: 881-890

    • DOI

      10.2353/ajpath.2009.080261

    • Related Report
      2011 Final Research Report
  • [Journal Article] Suppressive effect of orthovanadate on hepatic stellate cell activation and liver fibrosis in rats.2009

    • Author(s)
      Nishikawa Y, Ohi N, Yagisawa A, Doi Y, Yamamoto Y, etc.
    • Journal Title

      American Journal of Pathology 174

      Pages: 881-890

    • NAID

      120006658773

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mast cell leukemia with rapidly progressing portal hypertension.2009

    • Author(s)
      Yoshida M, Nishikawa Y, Yamamoto Y, Doi Y, etc.
    • Journal Title

      Pathology International 59

      Pages: 817-822

    • NAID

      10027382281

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Differential mRNA expression profiles in hepatocellular carcinomas induced by cirrhotic and non-cirrhotic protocols in mice2011

    • Author(s)
      西川祐司, ら
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 細胆管反応の細胞起源-マウス肝細胞追跡系を用いた検討2011

    • Author(s)
      永濱康晴,曽根正行,陳錫,岡田陽子,榎本克彦,西川祐司
    • Organizer
      第44回北海道病理談話会
    • Place of Presentation
      旭川
    • Year and Date
      2011-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝癌における肝細胞形質と胆管細胞形質の異常発現2011

    • Author(s)
      今了資,関智行,松尾康博,永濱康晴,陳錫,岡田陽子,西川祐司
    • Organizer
      第44回北海道病理談話会
    • Place of Presentation
      旭川
    • Year and Date
      2011-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胆管反応の細胞起源-マウス肝細胞追跡系を用いた検討2011

    • Author(s)
      永濱康晴, ら
    • Organizer
      第44回北海道病理談話会(北海道医学大会病理分科会)
    • Place of Presentation
      旭川
    • Year and Date
      2011-09-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 臓器別診断講習会「肝の非腫瘍性疾患」2011

    • Author(s)
      西川祐司, ら
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜(招待講演)
    • Year and Date
      2011-04-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝細胞および胆管上皮の分化におけるHNF-4αアイソフォームのスイッチング2011

    • Author(s)
      西川祐司,曽根正行,土井優子,大森泰文,吉岡年明,梅津哉,姜淑英,内藤眞,榎本克彦
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 肝細胞追跡系を用いた肝細胞の細胆管化生のin vivoにおける証明2011

    • Author(s)
      永濱康晴,曽根正行,陳錫,岡田陽子,吉岡年明,大森泰文,榎本克彦,西川祐司
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 肺高血圧症による高度うっ血肝にみられた小葉中心性の細胆管反応-肝傷害に伴う細胆管反応の病理学的考察2011

    • Author(s)
      西川祐司
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝転移周辺部および傷害肝における肝細胞でのheregulin発現の検討2011

    • Author(s)
      吉岡年明,西川祐司,山本洋平,大森泰文,南條博,榎本克彦
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] 成熟肝細胞由来の細胆管反応-肝細胞追跡系を用いた肝細胞の細胆管反応の証明2011

    • Author(s)
      永濱康晴,曽根正行,陳錫,岡田陽子,山本洋平,吉岡年明,大森泰文,榎本克彦,西川祐司
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 四塩化炭素およびDENにより誘導されたマウス肝癌のmRNA発現プロファイルの検討2011

    • Author(s)
      西川祐司,陳錫,永濱康晴,岡田陽子
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝転移および傷害肝における肝細胞でのheregulin発現の検討2011

    • Author(s)
      吉岡年明,西川祐司,山本洋平,大森泰文,南條博,榎本克彦
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] 蛋白チロシン脱リン酸化酵素阻害剤オルトバナジン酸のマウス肝発癌抑制効果に関する検討2010

    • Author(s)
      西川祐司, 永濱康晴, 他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝内・肝外胆管系の発生(シンポジウム)2010

    • Author(s)
      西川祐司, 曽根正行, 他
    • Organizer
      第17回肝細胞研究会
    • Place of Presentation
      秋田市
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分化転換後の肝細胞形質回復における副腎皮質ホルモンとサイトカインの相互作用2010

    • Author(s)
      曽根正行, 西川祐司, 他
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      東京都
    • Year and Date
      2010-04-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分化転換後の肝細胞形質回復における副腎皮質ホルモンとサイトカインの相互作用2010

    • Author(s)
      曽根ら
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管方向に分化転換した肝細胞の再成熟化2010

    • Author(s)
      曽根正行,西川祐司,大森泰文,吉岡年明,榎本克彦
    • Organizer
      第17回肝細胞研究会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝内・肝外胆管系の発生2010

    • Author(s)
      西川祐司,曽根正行,吉田正行,大森泰文,吉岡年明,榎本克彦
    • Organizer
      第17回肝細胞研究会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管上皮方向に分化転換した肝細胞の再成熟化2010

    • Author(s)
      曽根正行,西川祐司,大森泰文,吉岡年明,榎本克彦
    • Organizer
      第17回肝細胞研究会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 蛋白チロシン脱リン酸化酵素阻害剤オルトバナジン酸のマウス肝発癌抑制効果に関する検討2010

    • Author(s)
      西川祐司,永濱康晴,藤井瑞恵
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管系の発生と細胆管反応-肝細胞追跡系を用いた検討2009

    • Author(s)
      西川祐司, 榎本克彦
    • Organizer
      日本病理学会カンファレンス
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2009-07-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] 細胞質に局在するconnexin 32はHuH7肝癌細胞において癌幹細胞の自己複製を促進する2009

    • Author(s)
      川嵜洋平,大森泰文,西川祐司,吉岡年明,吉田正行,石川和夫,榎本克彦
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 前立腺細胞におけるTRAIL誘導アポトーシスに対するintegrin β4の役割2009

    • Author(s)
      吉岡年明,西川祐司,大森泰文,吉田正行,川嵜洋平,曽根正行,榎本克彦
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝細胞の胆管上皮への形質転換:その可逆性およびKupffer細胞由来サイトカインの影響2009

    • Author(s)
      曽根正行,西川祐司,大森泰文,吉岡年明,吉田正行,榎本克彦
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] マウス肝傷害における細胆管反応の検討2009

    • Author(s)
      西川祐司,曽根正行,大森泰文,吉岡年明,吉田正行,榎本克彦
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] マウス肝内・肝外胆管系の接合に関する発生学的検討2009

    • Author(s)
      西川祐司,曽根正行,吉田正行,大森泰文,吉岡年明,榎本克彦
    • Organizer
      第16回肝細胞研究会
    • Place of Presentation
      山形
    • Related Report
      2011 Final Research Report
  • [Presentation] 分化転換後の肝細胞形質回復に対する炎症性サイトカインの影響2009

    • Author(s)
      曽根正行,西川祐司,大森泰文,吉岡年明,榎本克彦
    • Organizer
      第16回肝細胞研究会
    • Place of Presentation
      山形
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管系の発生と細胆管反応-肝細胞追跡系を用いた検討2009

    • Author(s)
      西川祐司,榎本克彦
    • Place of Presentation
      つくば
    • Related Report
      2011 Final Research Report
  • [Presentation] Stemcell-independent ductular reaction andcarinogenenesis in the mouse liver

    • Author(s)
      Nishikawa Y, Sone M, Omori Y,Yoshioka T, Enomoto K
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.asahikawa-med.ac.jp/dept/mc/pathol1/index.htm

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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