胆固醇代谢稳态对细胞维持正常生命活动和生理功能至关重要。胆固醇代谢紊乱与非酒精性脂肪肝病、动脉粥样硬化、心脑血管病等密切相关。然而，胆固醇代谢相关疾病的发病机理仍存在很多未知。肝脏是胆固醇代谢的重要器官，为了寻找胆固醇代谢调控新分子，我们利用高脂高胆固醇饲喂树鼩，肝脏蛋白质组学数据发现，钙结合蛋白S100A11的表达与胆固醇饲喂浓度和时间正相关；S100A11促进胆固醇积累，提示S100A11是调控胆固醇代谢新分子，但其作用机制尚不清楚。因此，本项目计划开展：1）阐明S100A11是胆固醇代谢调控的新分子；2）探究S100A11在肝脏胆固醇代谢中的作用机制，其直接调控已知胆固醇代谢通路蛋白还是其它新的未知蛋白进而调控胆固醇代谢；3）评价S100A11在高胆固醇诱导的NAFLD中的重要性。本项目阐明S100A11调控胆固醇代谢的作用机制，为揭示胆固醇相关疾病的发病机理提供理论基础和防治策略。

Cholesterol homeostasis is critical for cell to maintain normal physiological activities. Dysfunction of cholesterol metabolism is associated with non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), cardiovascular and cerebrovascular diseases, and so on. However, up to now, the pathogenesis and precise mechanisms of these diseases are still largely unclear. The liver is an important organ for cholesterol metabolism. To find new molecules that may regulate cholesterol metabolism, tree shrews were fed with high fat and high cholesterol diet. Liver proteomic data revealed that the expression of calcium-binding protein S100A11 is increased in a time- and cholesterol concentration -dependent manner. Our preliminary data indicated that S100A11 promotes cholesterol accumulation, suggesting that S100A11 may be a new molecule regulating cholesterol metabolism, but its mechanism is unknown. Therefore, we propose this project to study: 1) To confirm S100A11 as a new molecule that regulates cholesterol metabolism in liver cells and mouse animal models; 2) To explore the mechanism of S100A11 in regulating liver cholesterol metabolism, whether S100A11 directly regulates cholesterol metabolism through the well-known pathways or other new unknown protein; 3) To evaluate the significance of S100A11 and its related molecules in mouse NAFLD induced with high cholesterol. The goal of this study is to illuminate the mechanism of S100A11 in regulating cholesterol metabolism, and provides a theoretical basis and prevention strategies to reveal the pathogenesis of cholesterol-related diseases.