2006 Fiscal Year Final Research Report Summary
The role of cytokine cascade in impaired liver regeneration and development of candidate pharmaceutical(s) to regulate this mechanism
| Project/Area Number |
16590585
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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 | Gifu University |
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Principal Investigator |
MORIWAKI Hisataka GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院医学系研究科, 教授 (50174470)
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| Project Period (FY) |
2004 – 2006
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| Keywords | TGF-β / impaired liver regeneration / cytokine / kallikrein / protease inhibitor / TNF-α / IFN-γ |
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| Research Abstract |
We conducted a study to investigate the mechanism of impaired liver regeneration induced by lipopolysaccharide (LPS) in mouse and obtained the following results.
1. LPS induces tumor necrosis factor-α(TNF-α), thereby activating plasma kallikrein. Plasma kallikrein cleaves latent transforming growth factor-β, that is produced hepatic stellate cells. Cleaved (or activated) TGF-β strongly inhibits liver regeneration.
2. The receptor responsible to this process is TNFR-1 but not TNFR-2 or Fas.
3. TNF-α also recruits heat shock protein (HSP) to stimulate liver fibrosis, while the mode of action by HSP is dual.
4. NIK-333, a candidate pharmaceutical under clinical development, reduces the emergence of TNF-α-positive oval cells and inhibits stellate cell activation. Thus, NIK-333 seems to be a promising compound to regulate the process as described above.
The role of cytokine cascade in impaired liver regeneration was elucidated in a series of experiments, and a candidate compound to regulate this mechanism was also identified.
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Author(s)
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Journal Title
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Author(s)
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Journal Title
J Biol Chem 279
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[Journal Article] Acyclc retinoid, NIK-333, inhibits N-diethyl nitrosamine-induced rat hepatocarcinogenesis through suppression of TGF-α expression and cell proliferation2004
Author(s)
Kagawa M, Sano T, Ishibashi N, Hashimoto M, Okuno M, Moriwaki H, Suzuki R, Kohno H, Tanaka T
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