| Project/Area Number |
06454263
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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 |
Gastroenterology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OKITA Kiwamu Yamaguchi University, First Department of Internal Medicine, Professor, 医学部, 教授 (70107738)
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| Co-Investigator(Kenkyū-buntansha) |
MASUHARA Masaaki Yamaguchi University, First Department of Internal Medicine, Postdoctoral fellow, 医学部・附属病院, 医員
SAKAIDA Isao Yamaguchi University, First Department of Internal Medicine, Assiatant Professor, 医学部・附属病院, 助手 (80263763)
安永 満 山口大学, 医学部, 講師 (90230234)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | hepatic regeneration / extracellular matrix / prolyl hydroxylase / 細胞外 マトリックス / プロリルハイドロキシラーゼ / コラーゲン / ハイドロキシプロリン |
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| Research Abstract |
One of the achievements during these 3 years is the finding that the expression of types III,and IV procollagen mRNA increased 2-3 fold at days of 3,7,4 compared with other days during the first 2 weeks after 70% partial hepatectomy. The time course of DNA synthesis in hepatocytes after partial hepatectomy detected by BrdU staining indicated that hepatic regeneration starts from the portal tract and progresses to the central vein. This result suggests that hepatic regeneration occurs not all at once but expands gradually like a wave. Also, pretreatment with proly 4-hydroxylase inhibitor, an agent inhibiting collagen synthesis, significantly suppressed hepatic DNA synthesis. Thus, extracellular matrix, e.g., collagens, is required for hepatic regeneration after partial hepatectomy. On the other hand, the injection of pig serum into rats can induce liver fibrosis by the activation of TGF-beta without hepatocytes cell death. In this model, treatment with pig serum reduced DNA synthesis about by 50% 24 h after partial hepatectomy compared with that untreated rats. Treatment with pig serum significantly increased the concentration of TGF-beta protein and the expression of type III pocollagen mRNA in the liver. Therefore, this result indicates that excessive production of extracellular matrix prevents hepatic regeneration. In the future, we plan to investigate whether addition of prolyl 4-hydroxylase inhibitor accelerates hepatic regeneration by inhibiting the excessive production of extracellular matrix.
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