2000 Fiscal Year Final Research Report Summary
Mechanism of hepertocyte differentiation by liver-enriched transcription factor network
| Project/Area Number |
10660316
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | Nagoya University |
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Principal Investigator |
ODA Hiroak Graduate School of Bioagricultural Sciences, NAGOYA UNIVERSITY, Associate Professor, 大学院・生命農学研究科, 助教授 (20204208)
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| Project Period (FY) |
1998 – 2000
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| Keywords | hepatocyte / primary culture / extracellular matrix / cell shape / HNF-4 / EHS-gel / liver-enriched transcription factors |
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| Research Abstract |
in vivo study of molecular mechanism of liver-specific gene expression
In order to determine how to determine liver-specific gene expression in liver, we measured liver-specific gene expression in regenerating liver. During regeneration of liver after partial hepatectomy, hepatectomized liver has to keep normal hepatocyte functions. Therefore, the hepatectomized liver enhances the liver-function as compared to usual. In regenerating liver, C/EBPβ is reported to be induced. And we found that HNF-4 gene expression was also induced after once dropped in regenerating liver. These results suggested that HNF-4 might be involved in maintenance of liver-function in regenerating liver.
Regulation of HNF-4 gene expression by cell shape
We reported that cell shape of hepatocytes was very important of maintenance of liver-specific function in cultured hepatocytes. And HNF-4 plays central role in cell shape dependent regulation of liver function. In signal transduction from cell shape to HNF-4 gene, microtuble was important. But microfilament and intermediate filament were not involved in cell shape-dependent regulation of HNF-4 gene expression. And microtuble network but not dynamic instability was responsible for the transmission of cell shape signal. After removal of microtuble disruption reagent, HNF-4 gene expression was markedly induced. Vanadate inhibited the induction of HNF-4 gene expression by the removal of the reagent. The results suggested that phosphorylation/dephosphorylation steps were crucial the HNF-4 induction by cell shape.
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