Elucidation of the clinical significance of autotaxin and lysophosphatidic acid in liver diseases.
| Project/Area Number |
17590618
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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 | The University of Tokyo |
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Principal Investigator |
IKEDA Hitoshi The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (80202422)
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| Co-Investigator(Kenkyū-buntansha) |
YATOMI Yutaka The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60200523)
TOMIYA Tomoaki The University of Tokyo, Faculty of Medicine, Project Lecturer, 医学部附属病院, 特任講師 (90227637)
YANASE Mikio The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助手 (50334397)
TEJIMA Kazuaki The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員 (30396733)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Autotaxin / Lysophosphatidic acid / Liver fibrosis / Liver cirrhosis / Liver damage |
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| Research Abstract |
The clinical significance of lysophosphatidic acid(LPA), a novel phospholipid mediator, and its synthetic enzyme, autotaxin(ATX) was investigated in liver damages. Serum ATX activity and plasma LPA level were determined to be elevated in human chronic liver diseases correlatively with fibrosis. Plasma LPA level was correlated with serum ATX activity, suggesting that serum ATX activity is one of the determinants of plasma LPA level. To investigate whether the enhancement of serum ATX activity and/or plasma LPA level might be generally found in liver damages, the study in animal models was performed. Serum ATX activity and plasma LPA level were enhanced in rats with chronic carbon tetrachloride(CCl_4) intoxication correlatively with fibrosis, where ATX mRNA expression was not altered in the liver of CCl_4-treated rats, indicating that enhancement of serum ATX activity may not be due to increased ATX production at the transcriptional level in the liver. Serum ATX activity and plasma LPA level were also increased in rats with acute liver injury due to dimethylnitrosamine intoxication or 70% hepatectomized rats. In rats with dimethylnitrosamine intoxication, serum ATX activity was correlated with serum ALT level, and in 70% hepatectomized rats, serum ATX activity was enhanced as early as 3 hours after the operation and sustained at the same level up to 24 hours after hepatectomy. These results suggest that serum ATX activity and plasma LPA level may be increased generally in liver damages in relation to the severity. The mechanism of enhancement of serum ATX activity in liver damages may involve the reduced clearance of ATX in damaged liver. Whether the increases of serum ATX activity and plasma LPA level may be simply the result of liver damages or the cause of liver damages should be further clarified.
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Report
(3 results)
Research Products
(3 results)
