2007 Fiscal Year Final Research Report Summary
The differentiating regulation from bone marrow stem cells and hepatic stem cells to hepatocytes and bile-duct cells as a tool of treatment against hepatic failure
| Project/Area Number |
17390103
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kobe University |
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Principal Investigator |
HAYASHI Yoshitake Kobe University, School of Medicine, Professor (50189669)
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| Co-Investigator(Kenkyū-buntansha) |
KU Yonson Kobe University, School of Medicine, Professor (40195615)
SEO Yasushi Kobe University, School of Medicine, Assistant Professor (90362772)
KANOMATA Naoki Kawasaki Medical University, Lecturer (60263373)
MASIWA Yoshimasa Kobe University, Graduate School of Medicine, Assistant Professor (50362778)
TSUJIMURA Tohru Hyogo College of Medicine, 医学部, Professor (20227408)
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| Project Period (FY) |
2005 – 2007
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| Keywords | SgIGSF / Oval cell / FoxO1 / Hepatocyte / Regenerative medicine / PI3-kinase / Akt / Diabetes Mellitus / Insulin resistance |
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| Research Abstract |
In fluminant hepatitis or Small Size for Graft cases, it is the most important that rapid recovery from liver failure is induced. Forkhead transcription factor FoxO mediates the function and differentiation of hepatocytes. And transfer from nuclear (active as a transcriptional nuclear protein) to cytoplasm (inactive) is controlled by PI3-kinase/Akt depending phosphorysation cascade. The new binding protein to FoxO1, P13, which is essential for adipocyte-differentiation and play an important role as a repressor of FoxO1, a transcriptional regulator and sensitizer of insulin, was found out. (J Clin Investigation 116(9): 2473-83, 2006; Diabetes in press; the 19^th Molecular Diabetology Symposium, Kobe).
SgIGSF is an intercellular adhesion molecule of the nectin-like family. In developing mouse liver, SgIGSF expression was transiently upregulated at perinatal ages and was restricted to the lateral membrane of biliary epithelial cells (BECs). To investigate the role of SgIGSF in bile duct/ductule formation, An in vitro model, in which rat hepatocyte aggregates embedded in collagen gels containing insulin and epidermal growth factor extend epithelial sheets and processes in the first week and form ductules within a month, was used. The process and ductular cells were continuously positive for SgIGSF and cytokeratin 19, a BEC marker. When the aggregate culture was started in the presence of a function-blocking anti-SgIGSF antibody, the number of epithelial processes per aggregate was reduced by 80%. These data suggests that SgIGSF is a novel and functional BEC adhesion molecule that is expressed for a limited time during active bile duct/ductule formation. (Hepatology, 45:684-694, 2007)
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