LSECtin调控kupffer细胞功能并影响非酒精性脂肪肝病的发生

Non-alcoholic fatty liver disease (NAFLD) is the major liver problem in developed countries. Kupffer cells play an important role in the development of NAFLD, but the specific molecular mechanisms are not very clear. Recently, we reported a novel c-type lectin, LSECtin (liver node sinusoidal endothelial cell lectin), which is specifically expressed on LSECs and Kupffer cells. LSECtin’s expression is IL-4 dependent, and IL-4 induces macrophages to polarize to M2 type. Recent experiments showed that LSECtin expression decreased in the high-fat diet-induced mouse NAFLD model liver. What’s more, M2-type related molecules IL-10 and MGL1 were downregulated, whereas M1-type related TNF-α and MCP1 expression were increased in LSECtin-/- mouse liver. So we raise a hypostasis that LSECtin may negatively regulate the inflammatory function of Kupffer cells, thereby inhibiting the occurrence of NAFLD. Therefore, this project intends to explore the mechanism of LSECtin’s regulation on Kupffer cell function, as well as LSECtin’s effect on obesity induced insulin resistance in NAFLD, for better understanding of the development of NAFLD and its new prevention propose.

非酒精性脂肪性肝病（NAFLD）现已成为欧美等发达国家和我国富裕地区最主要的慢性肝病。Kupffer细胞在NAFLD的发生发展中扮演重要角色，然而其具体分子机制很不明了。 本研究团队在前期发现了一种功能全新的蛋白LSECtin，主要表达在肝脏Kupffer细胞。其表达具有IL-4依赖的特性（IL-4能诱导巨噬细胞极化为M2型）。近期实验结果表明，在高脂饮食诱导的NAFLD小鼠模型中，肝脏LSECtin表达下降；而且LSECtin-/-小鼠肝脏中M2型相关分子IL-10与MGL1表达下调，而M1型相关分子TNF-α与MCP1表达上调。 我们推测：LSECtin可能负调节Kupffer细胞的炎症功能，进而抑制NAFLD的发生。因此本项目拟探索LSECtin对kupffer细胞功能调控机制以及是否影响NAFLD中肥胖诱导的胰岛素抵抗，为理解NAFLD的发生发展及其防治提出新思路。