| Project/Area Number |
24791433
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
TOSHIMA Takeo 九州大学, 医学(系)研究科(研究院), 共同研究員 (40608965)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 肝再生 / オートファジー / 老化 / 肝臓 / 肝切除 / 肝移植 |
|---|
| Research Abstract |
We investigated the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx) in liver-specific autophagy-related gene 5 (Atg5)-knockout mice. Liver regeneration was severely impaired by 70% PHx, with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx induced the intracellular ATP and beta-oxidation reduction, and injured cellular mitochondria. The accumulation of proteins marked with p62 or polyubiquitin indicated that the reorganization of intracellular proteins and organelles was impaired. Upregulation of p21 was associated with hepatocyte senescence, senescence-associated beta-galactosidase expression, irreversible growth arrest, and secretion of senescence-associated molecules, including interleukin-6/8. These findings indicate that autophagy plays a critical role in liver regeneration and in the preservation of cellular quality, preventing hepatocytes from becoming fully senescent and hypertrophic.
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