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尿外泌体 miRNA-615-3p 和 miRNA-3147 在糖尿病肾病中的表达及其与炎症和纤维化的关系。

Expression of urinary exosomal miRNA-615-3p and miRNA-3147 in diabetic kidney disease and their association with inflammation and fibrosis.

机构信息

Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Ren Fail. 2023 Dec;45(1):2121929. doi: 10.1080/0886022X.2022.2121929.

Abstract

BACKGROUND

Diabetic kidney disease (DKD) is one of the most common chronic complications of type 2 diabetes mellitus (T2DM), and it is particularly important to identify a high-quality method for evaluating disease progression. Urinary exosomes contain microRNA that might promise early diagnostic and monitoring markers of DKD. The present study aimed to identify novel exosome-related markers associated with inflammation and fibrosis to assess the progression of DKD.

METHOD

Exosomes were extracted from the urine of 83 participants to determine the expression levels of miRNA-615-3p and miRNA-3147 in 20 healthy people, 21 patients with T2DM and 42 patients with DKD, as determined by RT-qPCR. The circulating expression level of TGF-β1 was detected by ELISA. Serum Cystatin C was measured by a latex-enhanced immunoturbidimetric method. The correlation analyses were performed for all clinical and laboratory parameters.

RESULT

The expression level of urinary exosomal miRNA-615-3p in DKD patients was significantly higher than that in the control group and the T2DM group by RT-qPCR. The expression of miRNA-3147 showed an upward trend in the three groups of subjects, but it was not statistically significant. The urinary exosomal miRNA-615-3p was positively correlated with serum Cystatin C, plasma TGF-β1, creatinine, BUN, PCR and 24-h urine protein, and negatively correlated with eGFR and albumin. The diagnostic efficacy of urinary exosomal miRNA-615-3p combined with the ACR was higher than that of ACR alone.

CONCLUSIONS

Urinary exosomal miRNA-615-3p may be used as a novel biomarker for evaluating the progression of DKD, and may be involved in the process of inflammation and fibrosis in DKD. The combined diagnosis of urinary exosomal miRNA-615-3p and ACR may be used as more stable and sensitive diagnostic criteria for DKD.

摘要

背景

糖尿病肾病(DKD)是 2 型糖尿病(T2DM)最常见的慢性并发症之一,因此,寻找一种高质量的方法来评估疾病进展尤为重要。尿外泌体中含有 microRNA,可能成为 DKD 的早期诊断和监测标志物。本研究旨在寻找与炎症和纤维化相关的新型外泌体相关标志物,以评估 DKD 的进展。

方法

从 83 名参与者的尿液中提取外泌体,通过 RT-qPCR 确定 20 名健康人、21 名 T2DM 患者和 42 名 DKD 患者尿液中 microRNA-615-3p 和 microRNA-3147 的表达水平。通过 ELISA 检测 TGF-β1 的循环表达水平。通过乳胶增强免疫比浊法测量血清胱抑素 C。对所有临床和实验室参数进行相关分析。

结果

通过 RT-qPCR 发现,DKD 患者尿液中外泌体 microRNA-615-3p 的表达水平明显高于对照组和 T2DM 组。三组受试者中 microRNA-3147 的表达呈上升趋势,但无统计学意义。尿外泌体 microRNA-615-3p 与血清胱抑素 C、血浆 TGF-β1、肌酐、BUN、PCR 和 24 小时尿蛋白呈正相关,与 eGFR 和白蛋白呈负相关。尿外泌体 microRNA-615-3p 联合 ACR 的诊断效能高于 ACR 单独诊断。

结论

尿外泌体 microRNA-615-3p 可作为评估 DKD 进展的新型生物标志物,可能参与 DKD 的炎症和纤维化过程。尿外泌体 microRNA-615-3p 联合 ACR 的联合诊断可能作为更稳定、更敏感的 DKD 诊断标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/164b/9879181/aaed9029a97a/IRNF_A_2121929_F0001_C.jpg

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