Molecular dynamics of metabolism during perinatal liver development
| Project/Area Number |
23591566
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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 | Osaka University |
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Principal Investigator |
KONDOU Hiroki 大阪大学, 医学(系)研究科(研究院), 助教 (10373515)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Kazuko 大阪大学, 医学系研究科, 講師 (30294094)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | FGF19 / 胆汁うっ滞 / FGF21 / 低出生体重児 / DOHaD / 肝発生 / メタボリックシンドローム |
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| Research Abstract |
We studied FGF19 signaling pathway in chronic cholestasis using blood sample and liver tissue from Biliary atresia (BA) patients. Serum concentration of bile acid was significantly higher in BA patients, and their serum and tissue concentrations of FGF19 were significantly higher in BA patients. IHC and ISH revealed that FGF19 were aberrantly synthesized in hepatocytes in BA liver. While, those target gene, CYP7A1mRNA was not suppressed in BA patients despite of high concentration of bile acid and FGF19. Next, FXR mRNA was significantly up-regulated in hepatocytes in BA patients, and FGFR4 and KLB mRNA were also up-regulated. Further, phosphorylation of FGFR4 in BA patients was increased, then phosphorylation of ERK was decreased. Whereas, SHP mRNA, which suppress CYP7A1 was up-regulated in BA patients. These results suggest that FGF19 was aberrantly expressed in chronic cholestatic hepatocytes. however, this signal was not able to suppress CYP7A1 via ERK pathway.
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Sodium-coupled Neutral Amino Acid Transporter 4 Functions as a Regulator of Protein Synthesis during Liver Development2013
Author(s)
Hiroki Kondou, Masanobu Kawai, Kanako Tachikawa, Akihito Kimoto, Masayo Yamagata, Tomoko Koinuma, Miwa Yamazaki, Masahiro Nakayama, Sotaro Mushiake, Keiichi Ozono, Toshimi Michigami
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Journal Title
Hepatology Research
Volume: in press
Pages: 0-0
Related Report
Peer Reviewed
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[Journal Article] Humoral immunity is involved in the development of pericentral fibrosis after pediatric live donor liver transplantation.2012
Author(s)
Yamada H, Kondou H, Kimura T, Ikeda K, Tachibana M, Hasegawa Y, Kiyohara Y, Ueno T, Miyoshi Y, Mushiake S, Ozono K
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Journal Title
Pediatric Transplantation
Volume: 16
Issue: 8
Pages: 858-865
DOI
Related Report
Peer Reviewed
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[Presentation] Fibroblast growth factor 19 was aberrantly expressed in cholestatic hepatocytes, and its signal pathways were inappropriately downregulated in biliary atresia children.2013
Author(s)
Hasegawa Y, Kondou H, Kawai M, Ueno T, Miyahara Y, Konishi A, Nakao K, Tachibana M, Kimura T, Ikeda K, Bessho K, Miyoshi Y, Michigami T, Ozono K
Organizer
肝細胞研究会
Place of Presentation
大阪
Related Report
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[Presentation] Fibroblast growth factor 19 was aberrantly expressed in cholestatic hepatocytes, and its signal pathways were inappropriately down-regulated in biliary atresia children.2013
Author(s)
Hasegawa Y, Kondou H, Kawai M, Ueno T, Miyahara Y, Konishi A, Nakao K, Kimura T, Ikeda K, Tchibana M, Bessho K, Miyoshi Y, Michigami T, Ozono K.
Organizer
AASLD THE LIVER MEETING
Place of Presentation
Wahington DC, USA
Related Report
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