Molecular biological assessment of hepatocyte damage and fibrosis in intractable pediatric liver diseases
| Project/Area Number |
17591087
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
MUSHIAKE Sotaro Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (90291947)
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| Co-Investigator(Kenkyū-buntansha) |
KONDOU Hiroki Osaka Medical Center and Research Institute for Maternal and Children, Department of Environmental Medicine, Senior Researcher, 環境影響部門, 主任研究員 (10373515)
OZONO Keiichi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20270770)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Grb10 / Tyrosine kinase type receptor / Hepatic fibrosis / Hepatocyte damage / Hepatic stellate cell / SH2ドメイン / 肝硬変 / 偽胆管 |
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| Research Abstract |
The Grb10 expression in human pathological cirrhotic liver tissues and the animal models with liver damages were assessed. Dimethylnitrosamine (DMN) administration and CCI4 administration mice models were constructed according to the former reported protocol but they were not utilized for the following experiments because of their high lethality and hepatocyte damage rather than portal fibrosis. Then immunohistochemical staining for Grb10 was performed on the common bileduct ligation (CBDL) model, but no significant staining was obtained. Examination of mRNA expression by RT-PCR in the liver tissue of the CBDL mouse and the normal adult mouse demonstrated coordinative expressions of Grb10. The result was different from the former report that the Grb10 expression in the adult mouse liver was very low as compared with that in the embryo. On the other hand, in Western blot, protein expression in the adult mouse liver was very low compared to those in fetus and CBDL mouse liver.
Then hepatic parenchymal cells and hepatic stellate cells (HSC) were extracted from the rat liver, the mypfibroblastic transformation of HSC was assessed and the expressions of Grb10 were examined by RT-PCR. In result, the mRNA expressions were detected in myofibroblast (HSC), while very low in hepatocyte. In addition, mRNA expression was demonstrated in the damaged liver tissue of DMN-treated SD rats which is identical to the localization found in human cirrhotic liver. Though that does not reflect the pathological state in human cirrhotic liver, in vitro examination utilizing the cultured rat HSC can be a efficient tool for the assessment of the role of Grb10 in the mechanism of hepatic fibrosis in future.
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Report
(3 results)
Research Products
(7 results)
