TGF-β_(1)/Smad信号通路与肾间质纤维化  

TGF-β_(1)/Smad signaling pathway and renal interstitial fibrosis

作　　者：胡欣欣 孟晓凡 徐圣洁 郭兆安[2] HU Xinxin;MENG Xiaofan;XU Shengjie;GUO Zhaoan(The First Clinical School of Shandong University of Traditional Chinese Medicine,Ji'nan 250014,China;Department of Nephrology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Ji'nan 250014,China)

机构地区：[1]山东中医药大学第一临床医学院,济南250014 [2]山东中医药大学附属医院肾病科,济南250014

出　　处：《生命的化学》2023年第4期601-609,共9页Chemistry of Life

基　　金：山东省自然科学基金创新发展联合基金项目(ZR2022LZY005)。

摘　　要：肾间质纤维化(renal interstitial fibrosis,RIF)是慢性肾脏病(chronic kidney disease,CKD)的主要病理学基础,是CKD进展至终末期肾病的最终共同途径,与肾脏疾病的预后密切相关。RIF是多种信号通路相互作用的结果,其中转化生长因子(transforming growth factor,TGF)-β_(1)/small mothers against decapentaplegic(Smad)是RIF的主要信号转导通路,机体受到外来刺激后促进TGF-β_(1)与其受体结合并激活下游Smad蛋白参与RIF进程。TGF-β_(1)是RIF的中心介质并在所有类型肾脏细胞中广泛表达。Smad蛋白是目前已知的唯一的TGF-β受体的胞内基底酶物,其中,Smad3和Smad7失衡导致成纤维细胞激活和细胞外基质大量沉积是RIF进展的关键机制。TGF-β_(1)/Smad信号通路还可通过调控非编码RNA参与RIF进程。因此,靶向抑制TGF-β_(1)/Smad信号通路可作为RIF的潜在治疗策略。文章综述了TGF-β_(1)/Smad信号通路在RIF中的作用及通过阻断TGF-β_(1)并选择性抑制Smad信号传导治疗RIF的潜力,以期为临床诊疗RIF提供启发。Renal interstitial fibrosis(RIF)is the main pathological basis of chronic kidney disease(CKD),the final common way of CKD progression to end-stage renal disease,and closely related to the prognosis of kidney disease.RIF is the result of interaction of multiple signal pathways,among which transforming growth factor(TGF)-β_(1)/small mothers against decapentaplegic(Smad)is the main signal transduction pathway.When the body is stimulated by external stimuli,it promotes the binding of TGF-β_(1) and its receptor and activates downstream Smad proteins to participate in the process of RIF.TGF-β_(1) is the central mediator of RIF and is widely expressed in all types of renal cells.Smad protein is the only known intracellular substrate enzyme receptor of TGF-β_(1).The key mechanism of RIF progress is the imbalance of Smad3 and Smad7,which leads to the activation of fibroblasts and the deposition of extracellular matrix.TGF-β_(1)/Smad signaling pathway participates in RIF process by regulating noncoding RNA.Therefore,targeted inhibition of the TGF-β_(1)/Smad signaling pathway may serve as a potential therapeutic strategy for RIF.This paper summarizes the role of TGF-β_(1)/Smad signaling pathway in RIF and by blocking TGF-βand selectively inhibit the potential of Smad signal transduction therapy for RIF,so as to provide inspiration for clinical diagnosis and treatment of RIF.

关 键 词：肾间质纤维化 转化生长因子-β_(1)/small mothers against decapentaplegic 信号通路 非编码RNA 

分 类 号：R692[医药卫生—泌尿科学]