2002 Fiscal Year Final Research Report Summary
A long graft survival of the steatotic liver after the inhibition of chemokine production and the remodeling of the altered extracellular matrix
| Project/Area Number |
13670577
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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 |
Gastroenterology
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
YAMADA Shinwa U.O.E.H., School of Health Sciences, Professor, 産業保健学部, 教授 (60143426)
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| Project Period (FY) |
2001 – 2002
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| Keywords | liver transplantation / fatty liver / ischemia-reperfusion / neutrophil chemokine / extracellular matrix / mitochondrial function / hepatic macrophage |
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| Research Abstract |
The aim of this research project is to approach an effective strategy against the hepatic ischemia-reperfusion (IR) injury. The IR injury plays a crucial role in the primary non-function after hepatic transplantation using a steatotic graft.
Our group has previously found that in the alcoholic fatty liver a neutrophil-chemokine contributes to hepatocyte necrosis which is associated with apoptosis after IR (Hepatology 32:278, 2000). Additionally, in this model in vivo, the suppression of hepatic macrophage activity completely inhibits the production of the chemokine and protects the liver from the extensive necrosis after IR.
When we evaluated the above results, we fortunately found that a firm attachment of the chemokine with extracellular matrices was prerequisite for the neutrophil infiltration and inflammatory necrosis in the liver. In an in vivo study using primary hepatocytes, we had an evidence for a contribution of the altered mitochondrial function to hepatic apoptosis in fatty liver.
Thus, we raise three possible strategies for graft survival of the fatty livers as follows; 1. An inhibition of the chemokine production; 2. A remodeling of the extracellular matrix in the damaged liver; 3. An improvement of the mitochondrial function of the liver cells.
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Research Products
(12 results)
