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Investigation of aberrant regulation of bile acid, glucose, and lipid metabolism under chronic cholestatic state in pediatric liver disease.

Research Project

Project/Area Number 26461608
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKindai University (2015-2017)
Osaka University (2014)

Principal Investigator

KONDOU Hiroki  近畿大学, 医学部附属病院, 講師 (10373515)

Co-Investigator(Kenkyū-buntansha) 別所 一彦  大阪大学, 医学(系)研究科(研究院), 助教 (80423169)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords胆汁うっ滞 / CYP7A1 / FGF19 / 胆汁酸合成 / SPRY2 / HNF4α / microdisection / 胆道閉鎖症 / FGFR4 / KLB / 胆汁鬱滞
Outline of Final Research Achievements

Regulatory mechanisms of bile acid synthesis under chronic cholestasis remain unclear. We analyzed molecules involving bile acid metabolism using liver and serum samples from 8 biliary atresia (BA) children and 4 non-cholestatic disease controls. CYP7A1 mRNA expression was not inhibited in BA microdissected hepatocyte-entriched tissue despite high serum bile acid concentrations. The FGF19 protein was synthesized in BA hepatocytes, and its serum concentration was elevated. FGFR4 was phosphorylated in BA livers. However, ERK phosphorylation was significantly decreased. his is the first study to demonstrated that the FGF19 pathway did not suppress bile acid synthesis due to downregulation of ERK pathway in BA patients.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (1 results)

All 2015

All Presentation (1 results)

  • [Presentation] 胆道閉鎖症患者の肝臓では胆汁酸合成律速酵素CYP7A1の抑制機構の破綻が起きている2015

    • Author(s)
      長谷川泰浩、近藤宏樹
    • Organizer
      第32回日本小児肝臓研究会
    • Place of Presentation
      鳥取県米子市 鳥取大学医学部臨床講義棟3階431講義室
    • Year and Date
      2015-07-25
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2020-01-20  

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