2013 Fiscal Year Final Research Report

Impact of autophagy in liver regeneration

Research Project

Project/Area Number	24791433
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Digestive surgery
Research Institution	Kyushu University
Principal Investigator	TOSHIMA Takeo 九州大学, 医学(系)研究科(研究院), 共同研究員 (40608965)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	肝再生 / オートファジー
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.

(7 results)