2013 Fiscal Year Final Research Report

Molecular dynamics of metabolism during perinatal liver development

Research Project

Project/Area Number	23591566
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Pediatrics
Research Institution	Osaka University
Principal Investigator	KONDOU Hiroki 大阪大学, 医学(系)研究科(研究院), 助教 (10373515)
Co-Investigator(Kenkyū-buntansha)	WADA Kazuko 大阪大学, 医学系研究科, 講師 (30294094)
Project Period (FY)	2011 – 2013
Keywords	FGF19
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.