The impact of hepatocyte apoptosis and autophagy in the process of livercarcinogenesis
| Project/Area Number |
26253047
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
巽 智秀 大阪大学, 医学系研究科, 講師 (20397699)
疋田 隼人 大阪大学, 医学系研究科, 助教 (20623044)
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| Research Collaborator |
TANAKA Satoshi 大阪大学, 大学院医学系研究科
SAKANE Sadatsugu 大阪大学, 大学院医学系研究科
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥41,210,000 (Direct Cost: ¥31,700,000、Indirect Cost: ¥9,510,000)
Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2016: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2015: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2014: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
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| Keywords | 脂肪肝 / 肝細胞 / オートファジー / アポトーシス / Rubicon / 非アルコール性脂肪性肝疾患 / 消化器内科学 / 脂肪性肝疾患 |
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| Outline of Final Research Achievements |
We investigated autophagic change in the liver and the effect on liver apoptosis and lipid accumulation in NAFLD model. In liver cell lines, palmitic acid (PA) treatment suppressed autophagy with increase of Rubicon. Rubicon blockade attenuated autophagy impairment and reduced palmitate-induced apoptosis and lipid accumulation. The Rubicon increase by PA was caused by suppression of Rubicon degradation. Rubicon was also up-regulated in association with autophagy impairment in livers of mice fed a high-fat diet (HFD). Hepatocyte-specific Rubicon knockout mice showed amelioration of liver steatosis and injury as well as attenuation of autophagy impairment for four months HFD feeding. In humans, liver tissues obtained from patients with NAFLD expressed significantly higher levels of Rubicon than those without steatosis. Rubicon might be a new therapeutic target for NAFLD progression.
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice.2016
Author(s)
Tanaka S, Hikita H, Tatsumi T, Sakamori R, Nozaki Y, Sakane S, Shiode Y, Nakabori T, Saito Y, Hiramatsu N, Tabata K, Kawabata T, Hamasaki M, Eguchi H, Nagano H, Yoshimori T, Takehara T.
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Journal Title
Hepatology
Volume: 64
Issue: 6
Pages: 1994-2014
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Intake of high fat diet causes suppression of hepatocyte autophagy and enhancement of adipocyte autophagy and controls fat deposition of liver and adipose tissue2017
Author(s)
Sadatsugu Sakane, Hayato Hikita, Satoshi Tanaka, Yasutoshi Nozaki, Takahiro Kodama, Ryotaro Sakamori, Tomohide Tatsumi, Tsuyoshi Kawabata, Maho Hamasaki, Tamotsu Yoshimori, Tetsuo Takehara
Organizer
The 8th International Symposium on Autophagy
Related Report
Int'l Joint Research
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[Presentation] Autophagic changes of both adipose tissues and the liver induced by high fat diet feeding contribute to hepatic lipid accumulation2017
Author(s)
Sadatsugu Sakane, Hayato Hikita, Satoshi Tanaka, Kumiko Shirai, Naoki Mizutani, Yuta Myojin, Yuto Shiode, Yasutoshi Nozaki, Yoshinobu Saito, Tasuku Nakabori, Takahiro Kodama, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
Organizer
AASLD The Liver Meeting 2017
Related Report
Int'l Joint Research
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[Presentation] Enhanced expression of Rubicon inhibits autophagy and promotes apoptosis by increasing endoplasmic reticulum stress in nonalcoholic fatty liver disease.2015
Author(s)
Satoshi Tanaka, Hayato Hikita, Sadatsugu Sakane, Yasutoshi Nozaki, Yugo Kai, Tasuku Nakabori, Yoshinobu Saito, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
Organizer
The 66th Annual Meeting of the American Association for the study of Liver Disease
Place of Presentation
San Francisco, USA
Year and Date
2015-11-13
Related Report
Int'l Joint Research
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[Presentation] Increased expression of Rubicon protein by high fat diet suppresses autophagic flux and induces apoptosis by increasing endoplasmic reticulum stress in the pathogenesis of non-alcoholic fatty liver disease2014
Author(s)
Satoshi Tanaka, Hayato Hikita, Yasutoshi Nozaki, Yugo Kai, Tasuku Nakabori, Yoshinobu Saito, Ryotaro Sakamori, Takuya Miyagi, Naoki Hiramatsu, Tomohide Tatsumi, Tetsuo Takehara
Organizer
The 65th Annual Meeting of the American Association for the study of Liver Disease
Place of Presentation
Boston, USA
Year and Date
2014-11-09
Related Report
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