Impact of autophagy in liver regeneration

自噬对肝再生的影响

• 批准号: 23591989
• 负责人: YOSHIZUMI Tomoharu
• 金额: $ 3.33万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591989/
• 关键词: 肝臓外科学; オートファジー; 肝再生

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.

我们研究了肝特异性自噬相关基因5（Atg 5）敲除（KO）小鼠部分肝切除术（PHx）后肝再生中自噬相关通路的活性。70%PHx严重损害肝再生，术后有丝分裂减少，但肝细胞大小补偿性增加。PHx诱导细胞内腺苷三磷酸和β-氧化还原以及损伤的细胞线粒体。此外，Atg 5 KO小鼠中的PHx增强了p62和泛素化蛋白的肝脏蓄积。这些结果表明，在这些小鼠的再生肝脏中，自噬期间细胞内蛋白质和细胞器的重组受损。p21的上调与肝细胞衰老、衰老相关的β-半乳糖苷酶表达、不可逆的生长停滞和衰老相关分子（包括白细胞介素（IL）-6和IL-8）的分泌有关。