2004 Fiscal Year Final Research Report Summary
The modulation of transcription factor in liver regeneration after hepatic ischemia/reperfusion injury
| Project/Area Number |
15591381
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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 |
KATO Atsushi Chiba University, Department of General Surgery, Assistant Professor, 医学部附属病院, 助手 (70344984)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Department of General Surgery, Professor and Chairman, 大学院・医学研究院, 教授 (70166156)
YOSHIDOME Hiroyuki Chiba University, Department of General Surgery, Assistant Professor, 医学部附属病院, 助手 (10312935)
KUSOSAWA Hisashi Chiba University, Department of General Surgery, Stuff, 医学部附属病院, 医員 (10375678)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Ischemia / Reperfusion / Liver Regeneration / Transcription Factor / Damaged Liver / Cytokines / Chemokines |
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| Research Abstract |
1.Liver regeneration after hepatic ischemia/reperfusion injury.
Although there is abundant evidence to support the mechanisms of hepatic ischemia/reperfusion, much less is known about the role of regeneration of the liver after ischemia/reperfusion. I used C57BL/6 mice to assess the function of activin-follistatin system in hepatic regeneration after ischemia and reperfusion injury. The expression of mRNA for activin during a time course of liver ischemia/reperfusion was determined by real time PCR methods. Activin expression was increased within 1 hour of reperfusion. Serum levels of activin were also increased after early time point of reperfusion. Follistatin protein levels in serum samples increased just after activin protein levels. These results indicate that activin inhibits initiation of regeneration in hepatocytes at early time point after hepatic ischemia/reperfusion. The activin-follistatin system is one of the important regulatory systems modulating regeneration processes of
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the liver. Endogenous interleukin-13 protects hepatocytes and vascular endothelial cells during ischemia/reperfusion injury. Thus, an alternative possibility is that IL-13 directly regulates regeneration of the liver through hepatocytes and endothelial cells function.
2.Hepatic ischemia/reperfusion injury alterations in experimental cholestasis.
Previous studies from our laboratory have established that obstructive jaundice can increase the neutrophil infiltrates into the liver and significantly elevate hepatoceLLular injury after hepatic ischemia/reperfusion. Male C57BL/6 mice underwent ligation and division of the common bile duct to make obstructive jaundice. Obstructive jaundice mice are far more susceptible to 90 minutes ischemia than 30 minutes ischemia 7 day after surgery. NFκB activation and subsequent production of proinflammatory cytokines such as TNF-α were dramatically increased in obstructive jaundice mice in early time point after hepatic ischemia/reperfusion compared to sham controls. These findings demonstrate that obstructive jaundice develops inflammatory cascade through NFκB activation and renders liver susceptible to hepatic ischemia/reperfusion.
3.Clinical examination of hepatic ischemia/reperfusion injury
Postopertive levels of interleukin-6,interleukin-10,macrophage chemoattractant protein-1 and long hepatic ischemia were significantly correlated with postoperative surgical site infection and hepatocellular damage. Hepatic ischemia/reperfusion injury is potentially involved in the pathophysiology of postoperative infection and organ dysfunction. Less
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Research Products
(7 results)
