神经药理学报 ›› 2020, Vol. 10 ›› Issue (3): 54-64.DOI: 10.3969/j.issn.2095-1396.2020.03.010

• 综述 • 上一篇    

前列腺素受体4 与肾脏疾病相关性研究进展

熊梦瑶,贾英丽,杨宝学   

  1. 天然药物及仿生药物国家重点实验室,北京大学基础医学院药理学系,北京,100191,中国
  • 出版日期:2020-06-26 发布日期:2021-05-14
  • 通讯作者: 杨宝学,教授;研究方向:肾脏药理学;E-mail: baoxue@bjmu.edu.cn
  • 作者简介:熊梦瑶,博士研究生;研究方向:肾脏药理学;E-mail: mengyaoX1995@163.com
  • 基金资助:
    国家自然科学基金项目(No. 81620108029、No. 81974083)

Relationship between Prostaglandin Receptor EP4 and Renal Diseases

XIONG Meng-yao,JIA Ying-li,YANG Bao-xue   

  1. State Key Laboratory of Natural and Biomimetic Drugs & Department of Pharmacology,School of Basic Medical Sciences,Peking University,Beijing,100191,China
  • Online:2020-06-26 Published:2021-05-14
  • Contact: 杨宝学,教授;研究方向:肾脏药理学;E-mail: baoxue@bjmu.edu.cn
  • About author:熊梦瑶,博士研究生;研究方向:肾脏药理学;E-mail: mengyaoX1995@163.com
  • Supported by:
    国家自然科学基金项目(No. 81620108029、No. 81974083)

摘要:

前列腺素受体4(prostaglandin receptor 4,EP4)是内源性脂质介质前列腺素E2(prostaglandin E2,PGE2)的作用受体,属G-蛋白偶联受体(G protein coupled receptor,GPCR)的一种。EP4 在体内分布广泛,几乎在所有组织、脏器表达。在肾脏,肾小球旁颗粒细胞、肾小球上皮细胞、远曲小管和皮质集合管上皮细胞均有EP4 的高度表达。因EP4 可同时与Gs、Gi 蛋白途径偶联,与血管张力、氧化应激、炎症、细胞增殖等生理功能和病理生理过程密切相关。目前通过对全身性及肾组织特异性EP4 敲除小鼠模型的研究和选择性EP4 激动剂/拮抗剂的作用研究,证明EP4 在肾脏发挥重要作用,其PGE2-EP4 信号通路同时能产生保护和不良的影响。该
文将EP4 与肾脏疾病,包括肾性高血压、肾缺血/ 再灌注损伤、肾源性尿崩症、肾小球肾炎、肾小球硬化、慢性肾脏病及常染色体显性遗传性多囊肾病发生发展的相关性进行分析和总结。

关键词: 前列腺素受体4, EP4-Gs 激动剂/ 拮抗剂, EP4-Gi 激动剂/ 拮抗剂, 肾脏疾病

Abstract:

Prostaglandin receptor 4 (EP4) is the receptor of endogenous lipid medium prostaglandin E2 (PGE2) ,belongs to the G protein coupled receptor (GPCR) . EP4 is widely distributed in almost all tissues and organs in the body. In the kidney,there is high expression in the glomerular granulosa cells and epithelial cells,distal convoluted tubules and cortical collecting tubular cells. Because EP4 can be coupled with the Gs,Gi protein pathways at the same time,it is closely related to the physiological functions and pathophysiological processes,such as vascular tone,oxidative stress,inflammation,cell proliferation. Studies on systemic and renal specific EP4 knockout mice and the development of selective EP4 agonist/antagonist proved EP4 receptors play a key role in the kidney,the PGE2-EP4 signaling pathway can produce protective and adverse effects at the same time. This review article analyzes and summarizes the association of EP4 receptor in renal diseases,including renal hypertension,renal ischemia/reperfusion injury,nephrogenic diabetes insipidus,glomerulonephritis,glomerulosclerosis,chronic kidney disease and autosomal dominant polycystic kidney disease.

Key words: prostaglandin receptor 4, Gs, Gi, EP4 agonist/antagonist, kidney related diseases

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