2006 Fiscal Year Final Research Report Summary
Mechanism of sinusoidal endothelial cell proliferation and maturation during hepatic regeneration
| Project/Area Number |
17591375
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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 |
Digestive surgery
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| Research Institution | Chiba University |
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Principal Investigator |
SHIMIZU Hiroaki Chiba University, Graduate School of Medicine, General Surgery, Associate Professor, 大学院医学研究院, 講師 (80272318)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (70166156)
OHTSUKA Masayuki Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 助手 (90334185)
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| Project Period (FY) |
2005 – 2006
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| Keywords | liver regeneration / sinusoidal endothelial cell / Ito cell / hepatectomy |
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| Research Abstract |
AIMS : The regulatory mechanisms of sinusoidal regeneration after partial hepatectomy remain poorly understood.
METHODS : We investigated the expression of angiopoietin (Ang)-1, Ang- 2, Tie-2, and vascular endothelial growth factor (VEGF) in both regenerating liver tissue and isolated liver cells after 70% hepatectomy in rats. Proliferation and apoptosis of sinusoidal endothelial cells (SECs) were also evaluated with proliferating cell nuclear antigen (PCNA) and TUNEL staining, respectively.
Results : VEGF mRNA expression was increased with a peak at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and was increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 h and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2 was found in the SEC and hepatic stellate cell (HSC) fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h.
Conclusions : VEGF secreted by hepatocytes may play a key role in SEC proliferation, followed by increased Ang-1, presumably promoting sinusoidal maturation. Thereafter, Ang-2 mainly released from HSCs in the absence of VEGF may contribute to apoptosis of superfluous SECs for cessation of the regenerative process. Ang-Tie system, together with VEGF, plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy.
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Research Products
(10 results)
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[Journal Article] Aggressive surgical approach for Stage IV gallbladder carcinoma based on Japanese Society of Biliary Surgery Classification.
Author(s)
Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Nozawa S, Furukawa K, Mitsuhashi M, Takeuchi D, Suda K, Miyazaki M.
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Journal Title
Journal of Hepatobiliary-Pancreatic Surgery (in press)
Description
「研究成果報告書概要(欧文)」より
