肝细胞是一种高度极性特化的上皮细胞，细胞极性是肝脏功能和内稳态平衡的细胞活动基础。肝细胞结构和极性发生异常或丧失与肝脏功能紊乱和疾病如肝炎、肝癌有密切的内在关系。但由于研究水平和认识的局限和不足，目前对肝细胞极性的调控机制及其与细胞功能内在相关性了解甚少。本项目拟以细胞极性蛋白复合物Par3-Par6-aPKC及其关键结合蛋白Cdc42、Lgl为主要研究对象，利用已有的Cdc42、Par3和Lgl肝脏特异性敲除小鼠为模型，结合三维肝细胞培养体系，结合前期研究结果和近期最新发现，探讨细胞极性调控新机制；系统剖析Par复合物和Cdc42、Lgl在肝细胞极性建立和维持中的调控机制，阐明其内在调控规律，进而探讨其与肝代谢和胆汁酸稳态等功能的作用，揭示肝细胞极性与肝细胞代谢或肝内稳态的内在关系和调控规律，为肝疾病包括肝损伤-再生和肝癌病变的研究以及肝-血糖调控和组织器官间“对话”提供新的理论依据。

Hepatocyte is a polarized epithelial cell. Hepatocyte polarity is critical for liver function and homeostasis. Loss of hepatocyte polarity has been implicated in association withliver disease, such as cancer and hepatitis. Because of limitation of technology andshortage ofknowledge, the relationship between the polarity and the function of hepatocytes is not fully understood.This project will focus on the cell polarity complex Par3-Par6-aPKC and its binding protein, such as Cdc42 and Lgl. We will use the liver-specific knockout mice (Cdc42, Par3 and Lgl) and hepatocyte 3-D culture system as models to demostrate the mechanisms of cell polarity regulation. The roles of Par complex, Cdc42 and Lgl in establishing and maintaining of hepatocyte polarity will be systematically investegated. The mechanisms will be disclosed, which will reveal the relationships between hepatocyte polarity and liver metabolism or bile acids homeostasis. This study will provide new theory basis for liver diseases, including liver injury and regeneration, liver tumorigenesis, blood glucose regulation and the cross-talk between tissues.