摘要
造血前列腺素D合酶(hematopoietic prostaglandin D synthase,HPGDS)是一种谷胱甘肽转移酶,依赖于谷胱甘肽发挥活性作用,在巨核细胞系和多种免疫细胞中多有分布,广泛存在于多种组织,在过敏性疾病中发挥重要生物学功能。研究发现,HPGDS参与机体过敏反应的调控。HPGDS能够催化前列腺素H2(prostaglandin H2,PGH2)转化为前列腺素D2(prostaglandin D2,PGD2),PGD2和DP2受体结合,促进炎症因子的释放和过敏反应的发生。近年的研究发现,HPGDS在特应性皮炎(atopic dermatitis,AD)、食物过敏(food allergy)、过敏性鼻炎(allergic rhinitis)、过敏性哮喘(allelgic asthma)、嗜酸性食管炎(eosinophilic esophagitis,EoE)的发病中发挥重要作用,促进过敏反应和炎症性疾病的发生。HPGDS在不同疾病中发挥关键作用的细胞有所不同,HPGDS在特应性皮炎中的Th2细胞、过敏性哮喘中的肥大细胞、过敏性鼻炎和嗜酸性食管炎中的嗜酸性粒细胞中高表达,并在疾病的发生发展中发挥重要功能。值得注意的是,HPGDS可以作为治疗相关疾病的重要靶点,靶向HPGDS的药物,例如HQL-79、TAS-204、TAS-205、TFC-007等能够有效缓解存在HPGDS升高现象的多种过敏性疾病的症状。本文阐述了HPGDS的生物学功能,并综述了HPGDS在过敏性疾病中的重要作用和研究进展,以及HPGDS相关靶向药物研究,指出HPGDS在过敏性疾病发病中的重要性,为研发治疗过敏性疾病的药物提供新的思路。
Hematopoietic prostaglandin D synthase(HPGDS)is a glutathione-transferase enzyme that is widely distributed in a range of tissues and is found in megakaryocyte lineages as well as a number of immune cells.HPGDS has been identified to be involved in the regulation of allergic reactions in the body,accelerating the conversion of prostaglandin H2(PGH2)to prostaglandin D2(PGD2),and the binding of PGD2 to DP2 receptors increasing the release of inflammatory cytokines and the development of allergic reactions.In recent years,it has been discovered that HPGDS has a substantial role in allergic rhinitis,allergic asthma,eosinophilic esophagitis(EoE),and atopic dermatitis(AD).With Th2 cells in atopic dermatitis,mast cells in allergic asthma,eosinophilic granulocytes in allergic rhinitis and eosinophilic esophagitis,and other key players in various diseases,HPGDS plays a critical role in the pathogenesis of allergic reactions and inflammatory diseases and is essential for disease development.Notably,medications that target HPGDS such as HQL-79,TAS-204,TAS-205,and TFC-007 can effectively treat the symptoms of many allergy disorders in which HPGDS is excessive.HPGDS can be a significant target for the treatment of associated diseases.In order to highlight the significance of HPGDS in the pathogenesis of allergic diseases and to offer fresh ideas for the creation of medications for the treatment of allergic diseases,this paper describes the biological functions of HPGDS,reviews the important role and research progress of HPGDS in allergic diseases,as well as the experiments of HPGDS-related target drugs.
作者
樊易简
刘羽辰
初明
FAN Yi-Jian;LIU Yu-Chen;CHU Ming(Department of Immunology,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2024年第2期180-187,共8页
Chinese Journal of Biochemistry and Molecular Biology
基金
北大医学交叉研究种子基金研究项目(No.BMU2021MX021,BMU2022MX017)
北京大学基础医学院创新人才培养项目资助。
