肝活素HPS通过维持内质网稳态改善非酒精性脂肪性肝炎

内质网（endoplasmic reticulum，ER）稳态失衡与肝脏代谢、炎症、修复等密切相关，持续的ER应激（ER stress, ERS）会促进非酒精性脂肪性肝炎（Nonalcoholic steatohepatis, NASH）等多种肝病的发生发展。肝活素HPS是一种肝源性生长因子，可能在脂肪肝-脂肪性肝炎-肝癌的发生发展中发挥重要作用，其机制可能与ER稳态维持相关。本项目拟采用HPS基因敲除以及重组HPS蛋白处理等手段开展以下工作：（1）HPS对肝脏ERS的影响；（2）HPS调控ERS与肝脏脂代谢异常的关系；（3）ERS诱导HPS表达的分子机制；（4）HPS调控ERS的分子机制。目的是阐明HPS调控肝脏ERS的分子机制，评估HPS对肝脏ER稳态的维持在NASH发生发展中的作用，为NASH等肝脏疾病治疗提供新的思路。

Endoplasmic reticulum homeostasis is closely related to liver metabolism, inflammation, and repair. Continuous ER stress will promote the development of various liver diseases such as non-alcoholic steatohepatitis. HPS is a liver-derived growth factor, which may play an important role in the development of fatty liver-steatohepatitis-liver cancer, and its mechanism may be related to the maintenance of ER homeostasis. This project intends to use the methods of HPS gene knockout and recombinant HPS protein treatment to carry out the following work: (1) the effect of HPS on liver ERS; (2) The relationship between HPS regulation of ERS and liver lipid metabolism; (3) Mechanism of HPS expression induced by ERS; (4) The molecular mechanism of HPS regulating ERS. The purpose is to clarify the molecular mechanism of HPS regulating liver ERS, to evaluate the role of HPS in maintaining the homestasis of liver ER in the development of NASH, and to provide new ideas for the treatment of liver diseases such as NASH.