Role of Atg7 in Liver Damage and Regeneration

自噬是维持细胞内稳态和提供能量生成基质的主要细胞生存机制。它参与多种生理过程和许多病理条件，如癌症。在肝脏中，自噬调节蛋白质降解，并作为饥饿时的适应机制。此外，自噬有助于清除有毒分子，防止肿瘤形成。尽管如此，直到今天，自噬在癌症发展中仍具有双重功能：它可以阻止正常细胞中的肿瘤形成，并可以促进癌细胞的存活。然而，自噬调节肿瘤发生和发展的几个机制仍未得到解释。因此，需要更多的基础研究来进一步了解自噬调节的机制，并探索自噬调节在肝脏疾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是一种重要的自噬蛋白，是自噬体生物发生不可或缺的介质。我们计划利用Atg7缺陷小鼠，深入研究急性、中度和慢性肝损伤中，Chk2/p53/p21通路与Atg7在肝细胞和肝祖细胞增殖以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.