T细胞来源的细胞外囊泡通过miR-193a诱导足细胞损伤

doi:10.3969/j.issn.1006-298X.2018.02.005

肾脏病与透析肾移植杂志 ›› 2018, Vol. 27 ›› Issue (2): 124-129.DOI: 10.3969/j.issn.1006-298X.2018.02.005

T细胞来源的细胞外囊泡通过miR-193a诱导足细胞损伤

出版日期:2018-04-28 发布日期:2018-05-02

Circulating T cellderived extracellular vesicles induce podocyte injury through shuttling miR-193a

Online:2018-04-28 Published:2018-05-02

摘要/Abstract

摘要：

目的：探讨T细胞来源的循环细胞外囊泡（extracellular vesicles，EVs）中miR193a在局灶节段性肾小球硬化（FSGS）患者足细胞损伤中的作用。
方法：收集经肾活检确诊的FSGS患者和健康志愿者外周血，分离EVs。芯片和RTPCR筛选出患者 EVs中升高的microRNA （miRNA），再经体外足细胞试验，选出能导致足细胞骨架改变的miRNA。用目标miRNA转染T细胞系（Jurkat细胞），获得富集目标miRNA的EVs。给予Balb/c小鼠尾静脉注射Jurkat细胞EVs，测定尿蛋白/肌酐；用Jurkat细胞来源的EVs与足细胞共孵育，检测细胞骨架改变。验证miR193a损伤足细胞的分子机制。
结果：FSGS患者外周血EVs中miR193a水平明显上调，并能导致足细胞骨架损伤。FSGS患者循环EVs可导致小鼠蛋白尿和足细胞骨架结构紊乱。富含miR193a的Jurkat细胞EVs通过下调WT1，导致足细胞骨架结构损伤、诱导小鼠产生蛋白尿和足细胞足突融合。
结论：本研究发现FSGS患者循环中T细胞来源的EVs通过miR193a可诱导足细胞损伤。

关键词: 局灶节段性肾小球硬化, 细胞外囊泡, microRNA

Abstract:

Ｏｂｊｅｃｔｉｖｅ：To investigate the mechanism of Tcellderived extracellular vesicles (EVs) caused podocyte injury in FSGS and the injuryinducing miRNA.
Ｍｅｔｈｏｄｏｌｏｇｙ：EVs were isolated from biopsyproven FSGS patients and healthy controls plasma.MiRNAs differentially expressed in FSGS EVs were analyzed by chip arrays and RTPCR.Thirty milligrams EVs were injected into 8weekold male Balb/c mice through tail vein every other day.Urine albumin/creatinie was measured and kidney structure was analyzed after proteinuria occurred.EVs were also added to culture medium of podocytes.Podocyte cytoskeleton was measured.Jurkat cells were transfected with target miRNA to gain target miRNArich EVs.These EVs were injected into mice and added to cultured podocytes.
Ｒｅｓｕｌｔｓ：MiR193a is elevated in EVs from FSGS patients.EVs induced podocyte injury through miR193a induced down regulation of WT1.
Ｃｏｎｃｌｕｓｉｏｎ：Our results demonstrate a novel mechanism by which EVs induced podocyte injury through miR193a.

Key words: focal segmental glomerulosclerosis, extracellular vesicles, microRNA

张思盼，张昌明，吴俊男，等. T细胞来源的细胞外囊泡通过miR-193a诱导足细胞损伤[J]. 肾脏病与透析肾移植杂志, 2018, 27(2): 124-129.

ZHANG Sipan，ZHANG Changming，WU Junnan，et al. Circulating T cellderived extracellular vesicles induce podocyte injury through shuttling miR-193a[J]. Chinese Journal of Nephrology, Dialysis & Transplantation, 2018, 27(2): 124-129.

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ISSN 1006-298X CN 32-1425/R

T细胞来源的细胞外囊泡通过miR-193a诱导足细胞损伤

Circulating T cellderived extracellular vesicles induce podocyte injury through shuttling miR-193a

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