| Project/Area Number |
20390215
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 Institute of Physical and Chemical Research |
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Principal Investigator |
KOJIMA Soichi The Institute of Physical and Chemical Research, 分子リガンド生物研究チーム, チームリーダー (10202061)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Kanji 京都府立医科大学, 医学部付属病院, 研究員 (50381950)
KOSE Shingo 独立行政法人理化学研究所, 今本細胞核機能研究室, 専任研究員 (90333278)
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUURA Tomokazu 東京慈恵会医科大学, 医学研究科, 准教授 (30199749)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | Sp1, c-Met,アポトーシス / アルコール脂肪性肝炎 / トランスグルタミナーゼ / 架橋反応 / 小胞体ストレス / 非アルコール脂肪性肝炎 / Sp1 / c-Met / アポトーシス / 線維化 / マウスアルコール肝炎(ASH) / 非アルコール肝炎(NASH) / アルコール性肝炎 / 脂肪性肝炎 |
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| Research Abstract |
We demonstrated that upon injury, a protein crosslinking enzyme, transglutaminase translocates into the nucleus via its C-domain, crosslinks and inactivates Sp1 transcription factor, which results in the downregulation of the expression levels in c-Met, leading to caspase-independent hepatic cell death as well as fibrosis of the liver in both animal models and patients. We started screening of a unique compound that specifically inhibits nuclear translocation of transglutaminase.
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