Investigation of aberrant regulation of bile acid, glucose, and lipid metabolism under chronic cholestatic state in pediatric liver disease.
| Project/Area Number |
26461608
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kindai University (2015-2017)
Osaka University (2014) |
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Principal Investigator |
KONDOU Hiroki 近畿大学, 医学部附属病院, 講師 (10373515)
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| Co-Investigator(Kenkyū-buntansha) |
別所 一彦 大阪大学, 医学(系)研究科(研究院), 助教 (80423169)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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)
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| 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 |
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| 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.
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Report
(5 results)
Research Products
(1 results)
