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Role of Atg7 in Liver Damage and Regeneration

Atg7 在肝损伤和再生中的作用

基本信息

批准号：
262580368
负责人：
Privatdozentin Dr. Laura Elisa Buitrago Molina
金额：
--
依托单位：
Klinik für Gastroenterologie, Hepatologie und Endokrinologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/262580368?language=en
关键词：
Role Atg7 Liver Damage Regeneration

项目摘要

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.

自噬是维持细胞内环境稳定并提供能量产生的基质的主要细胞存活机制。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，并作为饥饿期间的适应机制。此外，自噬有助于清除有毒分子，防止肿瘤形成。然而，直到今天，自噬在癌症发展中具有双功能作用：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发生和发展的几种机制仍然无法解释。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脏疾病治疗中的应用前景。因此，本项目的目的是研究Atg 7在肝脏再生，肿瘤形成和免疫系统中的重要性。atg 7是一种重要的自噬蛋白，是自噬体生物合成不可或缺的介质。我们计划利用Atg 7缺陷小鼠，深入研究Chk 2/p53/p21通路与Atg 7在急性、中度和慢性肝损伤中肝细胞和肝祖细胞增殖以及免疫系统调节中的相互作用。