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 (2005-2006) GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院医学系研究科, 教授 (50174470)
奥野 正隆 (2004) 岐阜大学, 大学院・医学研究科, 助教授 (10204140)
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| Co-Investigator(Kenkyū-buntansha) |
森脇 久隆 岐阜大学, 大学院・医学研究科, 教授 (50174470)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | TGF-β / impaired liver regeneration / cytokine / kallikrein / protease inhibitor / TNF-α / IFN-γ / 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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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Augmentation of lipopolysaccharide-induced nitric oxide production by α-galactosylceramide in mouse peritoneal cells2005
Author(s)
Ito H, Koide N, Morikawa A, Hassan F, Islam S, Tumurkhuu G, Mori I, Yosida T, Kakumu S, Moriwaki H, Yokochi T
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Journal Title
J Endotoxin Res 11
Pages: 213-219
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Prevention of rat hepatocarcinogenesis by acyclic retinoid is accompanied by reduction in emergence of both TNF-a-expressing oval-like cells and activated hepatic stellate cells2005
Author(s)
Sano T, Kagawa M, Okuno M, Ishibashi N, Hashimoto M, Yamamoto M, Suzuki R, Kohno H, Kojima S, Friedman SL, Moriwaki H, Tanaka T
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Journal Title
Nutr Cancer 51
Pages: 197-206
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] The ring finger protein, RNF8, interacts with retinoid X receptor α and enhances its transcription-stimulating activity2004
Author(s)
Takano Y, Adachi S, Okuno M, Muto Y, Yoshioka T, Matsushima-Nishiwaki R, Tsurumi H, Ito K, Friedman SL, Moriwaki H, Kojima S, Okano Y
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Journal Title
J Biol Chem 279
Pages: 18926-18934
Description
「研究成果報告書概要(欧文)」より
Related Report
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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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Journal Title
Carcinogenesis 25
Pages: 979-985
Description
「研究成果報告書概要(欧文)」より
Related Report
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