ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2013, Vol. 22 ›› Issue (4): 309-314.

• 论文 • 上一篇    下一篇

循环microRNAs与局灶节段性肾小球硬化患者疾病活动的关系

  

  • 出版日期:2013-08-28 发布日期:2013-09-03

Circulating miRNAs and the disease activity of patients with focal segmental glomerulosclerosis

  • Online:2013-08-28 Published:2013-09-03

摘要:

摘要  目的:分析循环中与FSGS患者疾病活动相关的miRNAs,为后续探讨循环miRNAs在FSGS发病中的作用奠定基础。  方法:选取年龄、性别匹配的活动性FSGS患者及正常对照血浆各9例,提取血浆总RNA,采用TaqMan低密度芯片(TaqMan Low Density Array)进行miRNA表达谱分析,筛选出在活动性FSGS患者循环中表达上调的miRNAs分子。然后再选取32例活动性FSGS患者血浆,采用实时荧光定量逆转录聚合酶链反应(qRT-PCR)方法对筛选出的miRNAs分子进行验证。同时与非活动性FSGS患者进行比较。采用ROC曲线分析循环miRNA区分活动性FSGS与非活动性FSGS和正常对照的效能。  结果:与正常对照相比,活动性FSGS患者循环miR-125b, miR-186和miR-193a-3p水平显著上调(P<0.05)。ROC曲线分析显示,循环miR-125b, miR-186和miR-193a-3p区分活动性FSGS与正常对照的ROC曲线下面积(AUC)分别为0.882、0.789和0.910。与非活动性FSGS相比,活动性FSGS患者循环中miR-186水平也明显上调。  结论:活动性FSGS患者循环miR-125b, miR-186及miR-193a-3p较正常对照显著升高,其中miR-186的升高与疾病的活动性关系更密切。

关键词: 关键词 , 局灶节段性肾小球硬化 , 循环微小RNA , 疾病活动

Abstract:

ABSTRACT    Objective: To analyze the elationship between circulating miRNAs and the disease activity of patients with FSGS, and explore the role of circulating miRNAs in the pathogenesis of FSGS.  Methodology: miRNAs expression profile was performed on 2 pooled plasma samples from nine patients with active FSGS and 9 normal controls using TaqMan Low Density Array. A panel of differential expressed miRNAs were found, and then validated by quantitative reverse transcription PCR (qRT-PCR) array with individual plasma samples from 32 active FSGS patients. Meanwhile, plasma samples from 15 non-active FSGS patients were examined for candidate miRNAs. Receiver-operatin characteristic (ROC) curves were established to analyze the value of circulating miRNAs for differentiating active FSGS from non-active FSGS and healthy controls.   Results: The results of TaqMan Low Density Array indicated that a panel of miRNAs was deregulated in plasma of active FSGS patients. After large scale independent cohort validation by qRT-PCR, the levels of circulating miR-125b, miR-186 and miR-193a-3p were significantly increased in active FSGS patients compared with that in normal controls. ROC curve analysis showed that circulating miR-125b, miR-186 and miR-193a-3p was a significant value for differentiating active FSGS from normal controls. These miRNAs had an AUC of 0.882, 0.789 and 0.910, resepctively. In addition, the level of circulating miR-186 was also significantly increased in active FSGS patients when compared with non-active FSGS patients. Conclusions: We determined that the levels of circulating miR-125b, miR-186 and miR-193a-3p were increased in patients with active FSGS and miR-186 showed a more closer relationship with FSGS activity.

Key words: Key words: focal segmental glomerulosclerosis , circulating microRNA , disease activity