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SOX9 positive biphenotypic cell mediate ductular reaction with Notch signaling in Biliary atresia

Research Project

Project/Area Number 25462776
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionKumamoto University

Principal Investigator

Inomata Yukihiro  熊本大学, その他の研究科, 教授 (50193628)

Co-Investigator(Kenkyū-buntansha) SUDA HIROKO  熊本大学, 医学部附属病院, 非常勤診療医師 (40632659)
YOKOUCHI YUJI  福島県立医科大学, 医学部, 教授 (60252227)
SAKAMOTO SEISUKE  熊本大学, 医学部附属病院, 非常勤診療医師 (00378689)
Research Collaborator YOSHII DAIKI  熊本大学, 医学部附属病院, 大学院生
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords胆道閉鎖症 / SOX9遺伝子 / 細胆管反応 / 葛西手術 / 胆汁うったい / SOX9遺伝子 / Notch Signal / Sox9遺伝子 / 細胆管増生 / 肝線維化
Outline of Final Research Achievements

The mechanism of ductular reaction (DR) seen in liver diseases including biliary atresia (BA) has been still controversial. Notch signaling has been reported to involve in biliary development and differentiation in vivo. The aim was to elucidate the role of SOX9+ biphenotypic cells in DR and the association between Notch signaling and development of DR. Formalin fixed paraffin embedded liver sections from 47 liver specimens with BA were used. Image processing was performed by Image J 1.46 software after immunofluorescence staining. Sustained or progressive cholestasis led to decreasing of SOX9+HepPar1+ ratio and increasing CK19+ ratio, whereas reduction of jaundice led to increasing of SOX9+HepPar1+ ratio and decreasing CK19+ ratio. SOX9+HepPar1+ ratio had significant negative correlation with CK19+ ratio (r = -0.6, p = 0.002). In conclusion, DR in BA is mediated by SOX9+ biphenotypic cells, and Notch signaling is presumably required for development of DR.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] SOX)-positive hepatocytes mediate the progression of ductular reaction in biliary atresia2016

    • Author(s)
      Daiki Yoshii, Yuji Yokouchi, Hiroko Suda, Yukihiro Inomata
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 9

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] New insight into reactive ductular cells of biliary atresia provided by pathological assessment of SOX92014

    • Author(s)
      Suda H, Yoshii D, Yamamura K, Yokouchi Y, Inomata Y
    • Journal Title

      Pediatr Surg Int

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 乳児胆道閉鎖症に対する生体肝移植における門脈再建法と成績2015

    • Author(s)
      橋本晋太郎、吉井 大貴、猪股裕紀洋
    • Organizer
      日本小児栄養消化器肝臓学会
    • Place of Presentation
      広島
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 胆道閉鎖症で見られる増生細胆管とSOX9の関連についての検討2015

    • Author(s)
      吉井大貴、橋本晋太郎、猪股裕紀洋
    • Organizer
      日本小児栄養消化器肝臓学会
    • Place of Presentation
      広島
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 胆道閉鎖症における肝細胞の細胆管化生と線維化に対するSOX9の関与2015

    • Author(s)
      吉井大貴、横内裕二、須田博子、猪股裕紀洋
    • Organizer
      第52回日本小児外科学会学術集会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-05-28 – 2015-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 胆道閉鎖症における肝細胞の細胆管化生と線維化に関するSOX9の関与2015

    • Author(s)
      吉井大貴、横内裕二、須田博子、猪股裕紀洋
    • Organizer
      日本小児外科学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Significance of SOX9 gene for trans-differentiation of hepatocyte in liver2014

    • Author(s)
      吉井大貴、横内裕二、須田博子、猪股裕紀洋
    • Organizer
      熊本医学・生物科学国際シンポジウム
    • Place of Presentation
      熊本市医師会館
    • Year and Date
      2014-09-04 – 2014-09-05
    • Related Report
      2014 Research-status Report
  • [Presentation] 胆道閉鎖症における肝細胞の胆管細胞化生、肝線維化に対するSOX9遺伝子の関与についての検討2014

    • Author(s)
      吉井大貴、横内裕二、須田博子、猪股裕紀洋
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-04-03 – 2014-04-05
    • Related Report
      2014 Research-status Report
  • [Remarks] 熊本大学小児外科・移植外科のおける研究紹介

    • URL

      http://www2.kuh.kumamoto-u.ac.jp/ishoku/research/index.html

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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