| Project/Area Number |
17591390
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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 | Nagoya University |
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Principal Investigator |
NISHIO Hideki Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (30345897)
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| Co-Investigator(Kenkyū-buntansha) |
NIMURA Yuji Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80126888)
NAGINO Masato Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20237564)
ODA Koji Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (30311715)
YOKOYAMA Yukihiro Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (80378091)
湯浅 典博 名古屋大学, 医学部附属病院, 講師 (00303610)
江畑 智希 名古屋大学, 医学部附属病院, 助手 (60362258)
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | liver regeneration / continuous stretch in ECs / IL-6 / integrin / signaling cascade / surgical non-stress portal vein ligation model / STAT3 / 経皮経肝門脈塞栓術 / NF-kB / 類洞内皮細胞 / 持続伸展刺激 / インターロイキン6 |
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| Research Abstract |
We previously reported that an approximately 150% uni-axial sustained stretch in sinusoidal endothelial cells (ECs) after portal vein embolization (PVE) might be a trigger for liver regeneration via IL-6 secretion which is mediated by an activation of NF-kB. We then studied ECs cultured on an elastic silicone membrane and subjected to continuous uni-axial stretch. Our results indicate that continuous stretch-induced IL-6 secretion depends on outside-in signaling via integrins followed by a PI3-K/PLC-gamma/PKC/NF-kB signaling cascade.
Furthermore, we developed a non-stress portal vein ligation (nsPVL) rat model, which performs the ligation after surgical stress is subsided. After laparotomy under general anesthesia, a monofilament suture was placed around the left portal vein and knotted, but not tied, and the two ends were delivered through each flank. Seven days after laparotomy, PVL was created by pulling the two ends of the ligature, tightening the ligature. Biochemical assays indicated that the surgical stress of laparotomy resolved on day 7. The expression pattern of NF-kB and p-STAT3 was biphasic (first peak at 0.5-1 h, second peak at 3-6 h) in nsPVL model. IL-6 gene significantly increased 3 h after ligation in the non-embolized lobes. An expression of IL-6 mRNA in the sinusoidal ECs increased predominantly at the periportal area. The serum IL-6 concentration rose rapidly (within 3 h) after PVL and remained elevated until 6 h. Our results using nsPVL model may represent liver regeneration-associated signal pattern (PVE→(sinusoidal endothelial cell) stretch→NF→kB→IL-6→(hepatocyte)STAT3→liver regeneration cascade).
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