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细胞外囊泡中循环 miRNA 与特发性膜性肾病患者的治疗反应相关。

Circulating miRNAs in extracellular vesicles related to treatment response in patients with idiopathic membranous nephropathy.

机构信息

Division of Nephrology, Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Republic of Korea.

Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea.

出版信息

J Transl Med. 2022 May 14;20(1):224. doi: 10.1186/s12967-022-03430-7.

Abstract

BACKGROUND

Extracellular vesicle (EV)-microRNAs (miRNAs) are potential biomarkers for various renal diseases. This study attempted to identify the circulating EV-miRNA signature not only for discriminating idiopathic membranous nephropathy (IMN) from idiopathic nephrotic syndrome (INS), but also to predict the treatment response of patients with IMN.

METHODS

We prospectively enrolled 60 participants, including those with IMN (n = 19) and INS (n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum EV-miRNA profiles of all participants. To identify the EV-miRNAs predictive of treatment response in IMN, we also analyzed EV-miRNAs among patients with IMN with and without clinical remission.

RESULTS

The expression levels of 3 miRNAs differed between IMN patients, INS patients and HVs. In addition, compared to HVs, RNA sequencing revealed differential expression of 77 and 44 EV-miRNAs in patients with IMN without and with remission, respectively. We also identified statistically significant (|fold change ≥ 2, p < 0.05) differences in the expression levels of 23 miRNAs in IMN without remission. Biological pathway analysis of miRNAs in IMN without remission indicated that they are likely involved in various pathways, including renal fibrosis.

CONCLUSION

Our study identified EV-miRNAs associated with IMN as well as those associations with therapeutic response. Therefore, these circulating EV-miRNAs may be used as potential markers for the diagnosis and prediction of treatment response in patients with IMN.

摘要

背景

细胞外囊泡(EV)-microRNAs(miRNAs)是各种肾脏疾病的潜在生物标志物。本研究试图鉴定循环 EV-miRNA 特征,不仅可以区分特发性膜性肾病(IMN)和特发性肾病综合征(INS),还可以预测 IMN 患者的治疗反应。

方法

我们前瞻性地招募了 60 名参与者,包括 IMN(n=19)、INS(n=21)和健康志愿者(HV;n=20)。我们使用 RNA 测序评估了所有参与者的血清 EV-miRNA 图谱。为了鉴定 IMN 治疗反应的预测性 EV-miRNA,我们还分析了 IMN 患者中有无临床缓解的 EV-miRNA。

结果

IMN 患者、INS 患者和 HVs 之间的 3 种 miRNA 的表达水平不同。此外,与 HVs 相比,在 IMN 无缓解的患者中,RNA 测序显示了 77 种和 44 种 EV-miRNA 的差异表达,而在 IMN 缓解的患者中则分别显示了 44 种和 77 种 EV-miRNA 的差异表达。我们还发现了 IMN 无缓解患者中 23 种 miRNA 表达水平的统计学显著差异(|fold change≥2,p<0.05)。对 IMN 无缓解患者的 miRNA 进行生物通路分析表明,它们可能参与了各种通路,包括肾纤维化。

结论

我们的研究鉴定了与 IMN 相关的 EV-miRNAs 以及与治疗反应相关的 EV-miRNAs。因此,这些循环 EV-miRNAs 可能作为 IMN 患者诊断和预测治疗反应的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c9c/9107687/c43f813e9398/12967_2022_3430_Fig1_HTML.jpg

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