Impact of autophagy in liver regeneration

我们研究了肝脏特异性自噬相关基因5(ATG5)基因敲除(KO)小鼠肝部分切除(PHX)后肝再生中自噬相关通路的活性。70%的PHX严重损害了肝再生，术后有丝分裂减少，但肝细胞大小代偿性增加。PHX可诱导细胞内三磷酸腺苷和β-氧化还原，并损伤细胞线粒体。此外，在ATG5KO小鼠中，PHX增加了p62和泛素化蛋白在肝脏中的积累。这些结果表明，在这些小鼠的再生肝脏中，自噬过程中细胞内蛋白质和细胞器的重组受到了损害。P21的上调与肝细胞衰老、衰老相关的β-半乳糖苷酶的表达、不可逆的生长停滞以及衰老相关分子的分泌有关，包括白介素6和白介素8。

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.