Project/Area Number |
23591989
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Kyushu University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
SHIRABE Ken 九州大学, 医学研究院, 准教授 (70264025)
IKEGAMI Toru 九州大学, 医学研究院, 助教 (80432938)
YAMASHITA Yo-ichi 九州大学, 医学研究院, 助教 (00404070)
HARIMOTO Norifumi 九州大学, 医学研究院, 助教 (00419582)
UCHIYAMA Hideaki 九州大学, 医学研究院, その他 (70380425)
SOEJIMA Yuji 九州大学, 医学研究院, 共同研究員 (30325526)
NINOMIYA Mizuki 九州大学, 医学研究院, 助教 (30546461)
TAKETOMI Akinobu 九州大学, 医学研究院, 講師 (70363364)
MAEHARA Yoshihiko 九州大学, 医学研究院, 教授 (80165662)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 肝臓外科学 / オートファジー / 肝再生 |
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 (KO) mice. Liver regeneration was severely impaired by 70% PHx, with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx induced intracellular adenosine triphosphate and beta-oxidation reduction as well as injured cellular mitochondria. Furthermore, PHx in Atg5 KO mice enhanced hepatic accumulation of p62 and ubiquitinated proteins. These results indicated that reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver of these mice. Up-regulation of p21 was associated with hepatocyte senescence, senescence-associated b-galactosidase expression, irreversible growth arrest, and secretion of senescence-associated molecules, including interleukin (IL)-6 and IL-8.
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