| Project/Area Number |
23390197
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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 | Osaka University |
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Principal Investigator |
TAKEHARA Tetsuo 大阪大学, 医学(系)研究科(研究院), 教授 (70335355)
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| Co-Investigator(Kenkyū-buntansha) |
TATSUMI Tomohide 大阪大学, 大学院・医学系研究科, 助教 (20397699)
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| Co-Investigator(Renkei-kenkyūsha) |
HIKITA Hayato 大阪大学, 大学院・医学系研究科, 寄附講座助教 (20623044)
TANAKA Satoshi 大阪大学, 大学院・医学系研究科, 大学院生
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2011: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | オートファジー / 肝細胞癌 / アポトーシス / 非アルコール性脂肪肝炎 / 脂肪肝炎 / Atg7 / Mcl-1 / ノックアウトマウス / ソラフェニブ / Atg-7 |
|---|
| Research Abstract |
The aim was to clarify the relationship between apoptosis and autophagy in the pathogenesis of non-alcoholic steatohepatitis, and also in the treatment of hepatocellular carcinoma (HCC). Excess free fatty acids suppressed autophagic flux in hepatocytes and induced apoptosis by increasing endoplasmic reticulum stress. Hepatocyte-specific Mcl-1 knockout mice revealed that chronically increased hepatocyte apoptosis leads to liver fibrosis and cancer, suggesting that, in the pathogenesis of steatohepatitis, continuous hepatocyte apoptosis induced by autophagy impairment contributes to hepatic fibrogenesis and carcinogenesis. Finally, sorafenib, a multikinase inhibitor for the treatment of HCC, enhanced autophagic activity, which then inhibited apoptosis in hepatoma cells. In conclusion, autophagy may be a double-edged sword in the liver cancer development and progression; the promotion promotes the survival of the cancer cells while the restraint promotes the outbreak of cancer.
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