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血清外泌体miR-377-3p抑制视网膜色素上皮细胞增殖并为糖尿病性黄斑水肿提供生物标志物。

Serum exosomal miR-377-3p inhibits retinal pigment epithelium proliferation and offers a biomarker for diabetic macular edema.

作者信息

Jiang Li, Cao He, Deng Tingming, Yang Mingming, Meng Ting, Yang Huiqin, Luo Xiaoling

机构信息

Department of Ophthalmology, Shenzhen People's Hospital Second Clinical Medical College of Jinan University, Shenzhen, China.

出版信息

J Int Med Res. 2021 Apr;49(4):3000605211002975. doi: 10.1177/03000605211002975.

Abstract

OBJECTIVES

Diabetic macular edema (DME) is a complication of diabetes mellitus that leads to diabetic retinopathy. Thus far, the role of serum exosomal microRNAs (miRNAs) in DME progression remains elusive. This study investigated serum exosomal miRNAs from patients with type 2 diabetes (T2D) and DME to identify miRNAs associated with expression of vascular endothelial growth factor (VEGF), a pivotal component in DME progression; it also evaluated the diagnostic values of these miRNAs for DME.

METHODS

Serum was collected from patients with T2D who did (n = 20) and did not have DME (n = 24). Exosomes were isolated from serum and subjected to real-time polymerase chain reaction, western blotting, luciferase reporter, and miRNA profiling analyses.

RESULTS

VEGF was significantly upregulated in ARPE-19 cells treated with exosomes from patients with T2D and DME, compared with exosomes from patients with T2D alone. Among the top 10 downregulated miRNAs identified during exosomal miRNA profiling, miR-377-3p inhibited the expression of VEGF. Luciferase reporter assays confirmed that miR-377-3p could directly regulate VEGF expression. Receiver operating characteristic analysis identified serum exosomal miR-377-3p as a potential biomarker for DME.

CONCLUSION

Serum exosomal miR-377-3p inhibits VEGF expression to suppress retinal pigment epithelium proliferation and offers a diagnostic biomarker for DME.

摘要

目的

糖尿病性黄斑水肿(DME)是糖尿病的一种并发症,可导致糖尿病视网膜病变。迄今为止,血清外泌体微小RNA(miRNA)在DME进展中的作用仍不清楚。本研究调查了2型糖尿病(T2D)合并DME患者的血清外泌体miRNA,以鉴定与血管内皮生长因子(VEGF,DME进展中的关键成分)表达相关的miRNA;还评估了这些miRNA对DME的诊断价值。

方法

收集患有DME的T2D患者(n = 20)和未患DME的T2D患者(n = 24)的血清。从血清中分离出外泌体,并进行实时聚合酶链反应、蛋白质印迹、荧光素酶报告基因和miRNA谱分析。

结果

与仅来自T2D患者的外泌体相比,用T2D合并DME患者的外泌体处理的ARPE - 19细胞中VEGF显著上调。在外泌体miRNA谱分析中鉴定出的下调程度最高的前10种miRNA中,miR - 377 - 3p抑制VEGF的表达。荧光素酶报告基因检测证实miR - 377 - 3p可直接调节VEGF的表达。受试者工作特征分析确定血清外泌体miR - 377 - 3p为DME的潜在生物标志物。

结论

血清外泌体miR - 377 - 3p抑制VEGF表达以抑制视网膜色素上皮细胞增殖,并为DME提供了一种诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc6/8108084/127f881dd01e/10.1177_03000605211002975-fig1.jpg

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