Role of Atg7 in Liver Damage and Regeneration

自噬是维持细胞内稳态并为能量产生提供底物的主要细胞生存机制。它参与多种生理过程和众多的医学疾病，如癌症。在肝脏中，自噬调节蛋白质的降解，并在饥饿期间作为适应机制起作用。此外，自噬有助于清除防止肿瘤形成的有毒分子。然而，直到今天，自噬在癌症的发展中具有双重功能：它可以防止正常细胞中的肿瘤形成，并可以促进癌细胞的存活。然而，自噬如何调节肿瘤的启动和进展的几个机制仍然不清楚。因此，需要更多的基础研究来进一步了解自噬调控的机制，并探索自噬调控在肝病治疗中的应用前景。因此，本项目的目的是研究ATG7在肝脏再生、肿瘤形成和免疫系统中的重要性。ATG7是自噬蛋白在自噬小体发生过程中必不可少的介体。本研究拟利用ATG7基因缺陷小鼠，深入研究CHK2/P53/p21通路与ATG7在急、中、慢性肝损伤时肝细胞和肝祖细胞增殖及免疫系统调节中的相互作用。

Autophagy is a principal cell survival mechanism that sustains cellular homeostasis and provides substrates for energy generation. It is involved in multiple physiological processes and numerous phatological conditions such as cancer. In the liver, autophagy regulates protein degradation and contributes as adaptation mechanism during starvation. Additionally, autophagy helps to clear toxic molecules preventing neoplastic formation. Nevertheless, until today, autophagy has a bi-functional role in cancer development: it can prevent tumor formation in normal cells and can promote survival of cancer cells. However, several mechanisms of how autophagy modulates tumor initiation and progression are still unexplained. Therefore, more basic research is needed to further understand the mechanism of autophagy modulation and to explore future applications of autophagy regulation to the treatment of liver diseases. Consequently, the aim of this project is to study the importance of Atg7 in regeneration, tumor formation and immune system in the liver. Atg7 is an essential autophagy protein indispensable mediator for autophagosome biogenesis. Using Atg7-deficient mice, we plan to deeply investigate the interaction of Chk2/p53/p21 pathway with Atg7 in proliferation of hepatocytes and hepatic progenitor cells as well as modulation of immune system during acute, moderate and chronic liver injury.