IL-22调控FGF21表达及其影响非酒精性脂肪性肝病肝脏代谢功能的机制研究

IL-22 is a member of IL-10 family of cytokines. Its receptor, IL-22R1, is mainly expressed in skin, the digestive system and the respiratory system. Thus, IL-22 plays an crucial role in mucosal immunology and inflammation regulation. Additionally, IL-22 promotes cell regeneration and inhibit fibrosis of liver and lung. Previous studies reported that IL-22 ameliorated high fat diet-induced hepatic steatosis. However, the mechanism of IL-22 regulating glucose and lipid metabolism of liver remains largely unclear. It is well-known that FGF21 is an important regulatory factor in metabolism regulation. Our research showed that exogenous IL-22 promoted expression of FGF21 and changes of expression of metabolism-related genes ensued. Based on these studies, our study focuses on the role of IL-22 in regulation of FGF21 expression to study the effect of IL-22 on glucose and lipid metabolism in liver. We anticipate to reveal the mechanism of interaction between immune system and metabolic system. This study might be beneficial for exploring new targets and therapies for NAFLD and other metabolic syndrome.

IL-22是IL-10家族的成员之一，因其受体IL-22R1分布于皮肤、消化及呼吸系统，在粘膜免疫和炎症反应调控过程中发挥重要作用，并具有促进细胞生长、抑制纤维化等功能。研究发现，IL-22可减轻高脂喂养小鼠肝脏脂肪变性程度，改善肝脏代谢功能。然而IL-22对肝细胞糖脂代谢功能的调控机制仍不甚清楚。已知成纤维细胞生长因子21对机体糖脂代谢具有重要的调控作用。本项目前期研究发现，IL-22可显著上调人肝癌细胞系HepG2中FGF21的表达水平，并通过调控FGF21表达影响糖脂代谢相关基因的表达。因此本项目拟在此基础上研究IL-22对FGF21的调控作用和具体机制，深入探讨IL-22对肝脏糖脂代谢的影响。这有助于进一步了解免疫系统与代谢系统的相互调节作用与机制，并可能为非酒精性脂肪性肝病及其他代谢综合征的治疗和干预提供新的治疗策略和靶点。