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Molecular mechanisms regulating epithelial morphogenesis during the development of bile ducts

Research Project

Project/Area Number 22790386
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionSapporo Medical University

Principal Investigator

TANIMIZU Naoki  札幌医科大学, 医学部, 講師 (00333386)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords細胞 / 胆管上皮細胞 / 組織形成 / 幹細胞 / 3次元培養 / 上皮細胞 / 肝臓 / 胆管
Research Abstract

We revealed that α1-containing laminin regulated the lineage determination of cholangiocytes and the initial stage of bile duct morphogenesis, whereas α5-containing laminin contributes to the formation of mature duct structures. We also searched genes upregulated in mature cholangiocytes and identified a transcription factor grainyhead like 2(Grhl2). We introduced Grhl2 into HPPL, a liver progenitor cell line, and found that Grhl2 enlarged the central lumen of cysts. We further found that Grhl2 enhanced barrier function of the monolayer of HPPL and upregulated expression of Claudin3, Claudin4, and Rab25. Thus, we conclude that Grhl2 promotes the maturation of epithelial lumen by governing the molecular network among Clandin3, Claudin4, and Rab253.

Report

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

    (21 results)

All 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (16 results) Remarks (1 results)

  • [Journal Article] Growth ability and repopulation efficiency of transplanted hepatic stem, progenitor cells, and mature hepatocytes in retrorsine-treated rat livers2012

    • Author(s)
      Ichinohe N, Kon J, Sasaki K, Nakamura Y, Ooe H, Tanimizu N, Mitaka T
    • Journal Title

      Cell Transplant

      Volume: 21 Issue: 1 Pages: 11-22

    • DOI

      10.3727/096368911x580626

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proliferation of rat small hepatocytes depends on follistatin expression2012

    • Author(s)
      Ooe H, Chen Q, Kon J, Sasaki K, Miyoshi H, Ichinohe N, Tanimizu N, Mitaka T
    • Journal Title

      J Cell Physiol

      Volume: 227 Issue: 6 Pages: 2363-2370

    • DOI

      10.1002/jcp.22971

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver stem/progenitor cells : their characteristics and regulatory mechanisms.2011

    • Author(s)
      Tanaka M, Itoh T, Tanimizu N, Miyajima A
    • Journal Title

      J Biochem

      Volume: 149(3) Issue: 3 Pages: 231-239

    • DOI

      10.1093/jb/mvr001

    • NAID

      10030583627

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver stem/progenitor cells : their characteristics and regulatory mechanisms2011

    • Author(s)
      田中稔、谷水直樹, 他
    • Journal Title

      Journal of Biochemistry

      Volume: 149 Pages: 231-239

    • NAID

      10030583627

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Differentiation potential of cholangiocytes Liver Down Under2011

    • Author(s)
      谷水直樹、三高俊広
    • Place of Presentation
      オーストラリアパース
    • Year and Date
      2011-11-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Differentiation potential of cholangiocytes2011

    • Author(s)
      Tanimizu N
    • Organizer
      Liver Down Under : Liver development, diseases & regeneration
    • Place of Presentation
      Perth, Australia
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 転写因子Grhl2は上皮バリア機能および上皮細胞の形態形成を制御する2011

    • Author(s)
      谷水直樹、千賀一徳、三高俊広、宮島篤
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 発生過程における胆管上皮細胞の分化能の変化2011

    • Author(s)
      谷水直樹、三高俊広
    • Organizer
      第44回北海道病理談話会
    • Place of Presentation
      旭川市国際会議場
    • Year and Date
      2011-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 発生過程における胆管上皮細胞の肝細胞分化能の変化2011

    • Author(s)
      谷水直樹
    • Organizer
      第44回北海道病理談話会
    • Place of Presentation
      旭川市国際会議場
    • Year and Date
      2011-09-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胆管上皮細胞に特異的な転写因子Grhl2の機能解析2011

    • Author(s)
      千賀一徳、谷水直樹、三高俊広、宮島篤
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Year and Date
      2011-06-24
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 胆管上皮細胞の肝細胞分化能の検討2011

    • Author(s)
      谷水直樹、三高俊広
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Year and Date
      2011-06-24
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管上皮細胞に肝細胞分化能の検討2011

    • Author(s)
      谷水直樹
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Year and Date
      2011-06-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胆管上皮細胞の分化能の検討2011

    • Author(s)
      谷水直樹、三高俊広
    • Organizer
      第10回再生医療学会
    • Place of Presentation
      新宿京王プラザ
    • Year and Date
      2011-03-02
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管上皮細胞の肝細胞分化能の検討2011

    • Author(s)
      谷水直樹
    • Organizer
      第10回再生医療学会
    • Place of Presentation
      新宿京王プラザホテル
    • Year and Date
      2011-03-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of laminins in bile duct morphogenesis2011

    • Author(s)
      谷水直樹、宮島篤、三高俊広
    • Organizer
      Keystone Symposia
    • Place of Presentation
      カナダバンクーバー
    • Year and Date
      2011-01-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of laminins in bile duct morphogenesis2011

    • Author(s)
      谷水直樹
    • Organizer
      Keystone symposium
    • Place of Presentation
      カナダ バンクーバー
    • Year and Date
      2011-01-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 上皮細胞による組織形成を制御する因子についての研究2010

    • Author(s)
      谷水直樹、宮島篤、三高俊広
    • Organizer
      第32回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] 上皮細胞による組織構造形成を制御する因子についての研究2010

    • Author(s)
      谷水直樹
    • Organizer
      第32回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝臓の胆管上皮細胞の分化や胆管構造形成を制御する因子についての研究2010

    • Author(s)
      谷水直樹、三高俊広
    • Organizer
      第43回北海道病理談話会
    • Place of Presentation
      北海道大学医学部学友会館フラテ
    • Year and Date
      2010-10-30
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 胆管の構造形成を制御する因子についての研究2010

    • Author(s)
      谷水直樹、千賀一徳、宮島篤、三高俊広
    • Organizer
      第17回肝細胞研究会
    • Place of Presentation
      秋田アトリオン
    • Year and Date
      2010-06-18
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Remarks]

    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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