游离脂肪酸受体4作为呼吸系统疾病潜在治疗靶点研究进展

Research progress of free fatty acid receptor 4 as a potential therapeutic target for respiratory system diseases

游离脂肪酸受体4(FFAR4)作为G蛋白偶联受体家族的一员,与长链脂肪酸结合而调节机体糖脂代谢、激素分泌、炎性反应等多种病理生理过程,是治疗糖脂代谢紊乱及免疫介导疾病的热门靶点。近年来,多项国内外研究发现,激活后的FFAR4可通过募集β-抑制蛋白2(β-arrestin2)而调控下游多种信号通路抑制炎性反应,介导受体内化为FFAR4/β-arrestin2信号复合物,抑制Toll样受体4(TLR4)重组蛋白和肿瘤坏死因子-α(TNF-α)等诱导的促炎信号,发挥抗炎作用,有望成为呼吸系统慢性炎症性疾病的潜在治疗靶点。该文总结了FFAR4的结构功能、信号传导及其在哮喘和慢性阻塞性肺疾病(COPD)等疾病中的研究现状,旨在揭示FFAR4调控气道炎症的分子机制,为呼吸系统慢性炎症性疾病的治疗扩展新视野。

Free fatty acid receptor 4(FFAR4),as a member of G protein-coupled receptor family,is combined with long-chain fatty acids to regulate a variety of pathophysiological processes such as glucose and lipid metabolism,hormone secretion and inflammation reaction,and is a hot target for the treatment of glucose and lipid metabolism disorders and immune-mediated diseases.In recent years,a number of domestic and foreign researches find that activated FFAR4 regulates a variety of downstream signal pathways to inhibit inflammation by recruitingβ-arrestin2,mediate the receptor conversion to FFAR4/β-arrestin2 signaling complex and inhibit the pro-inflammatory signal induced by TLR4 recombinant protein and TNF-αto play the role of anti-inflammation,which is expected to become a potential research target for the prevention and treatment of chronic inflammatory diseases of the respiratory system.This review summarizes the structure,function and signal transduction of FFAR4 and its research status quo in asthma and chronic obstructive pulmonary disease(COPD),in order to reveal the molecular mechanism of FFAR4 regulating airway inflammation and expand a new field of vision for the treatment of chronic inflammatory diseases of respiratory system.