异三聚体G蛋白与足细胞损伤  

Role of heterotrimer G protein in podocyte injury

作　　者：刘灿 戴恩来 丁照然 段淑文 王晓辉 LIU Can;DAI Enlai;DING Zhaoran;DUAN Shuwen;WANG Xiaohui(School of Traditional Chinese and Western Medicine,Gansu University of Chinese Medicine,Lanzhou 730030,Gansu,China;Department of Nephrology,Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730030,Gansu,China)

机构地区：[1]甘肃中医药大学中西医结合学院,甘肃兰州730030 [2]甘肃中医药大学附属医院肾病科,甘肃兰州730030

出　　处：《中国临床药理学与治疗学》2024年第2期177-187,共11页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(82160852);甘肃省教育厅优秀研究生“创新之星”基金资助项目(2023CXZX-738)。

摘　　要：G蛋白偶联受体(G protein-coupled receptor,GPCRs)是人体内最大的膜蛋白受体超家族,共有超过800种亚型,目前约有35%经食品药品监督管理局批准上市的药物靶向GPCRs治疗多种疾病,如心力衰竭(β肾上腺素受体)、消化性溃疡(组胺受体)、前列腺癌(促性腺激素受体)、高血压(肾上腺素能和血管紧张素受体)、疼痛(阿片受体)和支气管哮喘(β2肾上腺素受体)等。虽然GPCRs数量巨大,但其下游的信号蛋白却是有限的,异三聚体G蛋白(heterotrimeric G proteins,GPs)是传导GPCRs信号的关键蛋白,通过与GPCRs偶联将细胞外刺激转化为细胞内反应并通过下游级联启动多种信号转导事件。足细胞是肾小球滤过屏障的重要组成部分,其损伤是蛋白尿形成和肾小球进行性硬化的核心事件。本文就GPs的调控、信号转导及其在足细胞损伤中的作用等方面作一综述,以期为科研和临床研治该病提供理论依据。GPCRs are the largest membrane pro-tein receptor superfamily in the human body,with more than 800 isoforms,and approximately 35%of Food and Drug Administration-approved and mar-keted drugs currently target GPCRs for the treat-ment of a wide range of diseases,for heart failure(beta-adrenergic receptors),peptic ulcer(histamine receptors),prostate cancer(gonadotropin recep-tors),hypertension(adrenergic and angiotensin re-ceptors),pain(opioid receptors),and bronchial asthma(beta2-adrenergic receptors)examples.Al-though the number of GPCRs is enormous,the sig-naling proteins downstream of them are limited,heterotrimeric G proteins(GPs)are key proteins that signal GPCRs,translate extracellular stimuli in-to intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades.Podocytes are an important component of the glomerular filtration barrier,and their dam-age is a central event in proteinuria formation and progressive glomerulosclerosis.This article reviews the regulation of GPs,their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this dis-ease.

关 键 词：G蛋白偶联受体 异三聚体G蛋白 足细胞损伤 

分 类 号：R511[医药卫生—内科学]