细胞外囊泡衍生的 miR-26b-5p 在糖尿病视网膜病变患者的血清中上调。

Extracellular Vesicle-Derived miR-26b-5p is Up-Regulated in the Serum of Patients with Diabetic Retinopathy.

机构信息

Department of Ophthalmology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264100, P.R. China.

Department of Ophthalmology, Yantaishan Hospital, Yantai, Shandong, 264100, P.R. China.

出版信息

Comb Chem High Throughput Screen. 2022;25(5):877-882. doi: 10.2174/1386207324666210216092917.

DOI:10.2174/1386207324666210216092917

PMID:33593252

Abstract

BACKGROUND

Diabetic retinopathy (DR) is a severe complication of diabetes; however, the pathogenesis of DR has not been completely clarified, which is mostly dependent on the molecular pathology. This study aimed to investigate key serum-derived miRNAs associated with DR.

METHODS

miRNA expression profile arrays of human umbilical vein endothelial cells (HUVECs) treated with glucose were downloaded from the Gene Expression Omnibus (GEO) database (GSE74296). Weighted gene co-expression network analysis (WGCNA) was performed to obtain hub miRNAs, which were verified in HUVECs treated with 40 mM and 5 mM glucose, respectively. Meanwhile, serum samples of patients with DR and healthy controls were collected, and EVs were extracted from the patients' serum by ultracentrifugation. Hub miRNAs associated with endothelial dysfunction were verified in healthy individuals before and after treatment of patients with DR, by qRT-PCR.

RESULTS

These miRNAs were categorized into six modules, among which miR-26b-5p had a strong association with other modules. This miRNA was also one of the hyperglycemia-induced miRNAs related to endothelial dysfunction. miR-26b-5p was up-regulated in HUVECs treated with 40 mM glucose and in the serum of patients with DR before and after treatment. Furthermore, miR- 26b-5p was slightly up-regulated in serum-derived EVs but not in serum without EVs in DM patients.

CONCLUSION

Our results suggest that EVs derived from miR-26b-5p are up-regulated in the serum of patients with DR.

摘要

背景

糖尿病视网膜病变（DR）是糖尿病的一种严重并发症，但 DR 的发病机制尚未完全阐明，主要依赖于分子病理学。本研究旨在探讨与 DR 相关的关键血清来源的 miRNA。

方法

从基因表达综合数据库（GEO）（GSE74296）中下载经葡萄糖处理的人脐静脉内皮细胞（HUVEC）的 miRNA 表达谱阵列。进行加权基因共表达网络分析（WGCNA）以获得关键 miRNA，分别在 40mM 和 5mM 葡萄糖处理的 HUVEC 中进行验证。同时，收集 DR 患者和健康对照者的血清样本，并通过超速离心从患者血清中提取 EVs。通过 qRT-PCR 验证与血管内皮功能障碍相关的健康个体患者治疗前后的关键 miRNA。

结果

这些 miRNA 被分为六个模块，其中 miR-26b-5p 与其他模块有很强的关联。该 miRNA 也是与内皮功能障碍相关的高血糖诱导的 miRNA 之一。在 40mM 葡萄糖处理的 HUVEC 中以及 DR 患者治疗前后的血清中，miR-26b-5p 上调。此外，在 DM 患者的血清中，miR-26b-5p 在 EVs 衍生的血清中略有上调，但在无 EVs 的血清中没有上调。