人脐带间充质干细胞来源的外泌体 microRNA-17-3p 通过靶向 STAT1 改善糖尿病视网膜病变小鼠的炎症反应和抗氧化损伤。

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-17-3p ameliorates inflammatory reaction and antioxidant injury of mice with diabetic retinopathy via targeting STAT1.

机构信息

Department of Ophthalmology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518000, Guangdong, China.

出版信息

Int Immunopharmacol. 2021 Jan;90:107010. doi: 10.1016/j.intimp.2020.107010. Epub 2020 Dec 14.

DOI:10.1016/j.intimp.2020.107010

PMID:33333415

Abstract

BACKGROUND

Accumulating evidence has reported the role of microRNA (miR) on diabetic retinopathy (DR). Thus, the aim of the study was to investigate the effect of exosomal miR-17-3p targeting signal transducer and activator of transcription 1 (STAT1) on inflammatory reaction and antioxidant injury of DR mice.

METHODS

A mouse diabetes model was established and injected with miR-17-3p-containing human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes to ascertain the role of exosomal miR-17-3p. The blood glucose, glycosylated hemoglobin (HbAlc), weight, hemoglobin (Hb) content, inflammatory factors, oxidative stress factors, vascular endothelial growth factor (VEGF), apoptosis index and glutamine synthetase (GS) level in serum and/or retinal tissues of DR mice were measured. miR-17-3p and STAT1 expression in retinal tissues as well as the target relationship between miR-17-3p and STAT1 were tested.

RESULTS

miR-17-3p decreased and STAT1 increased in retinal tissues of DR mice, and STAT1 was the target gene of miR-17-3p. Injection of up-regulated exosomal miR-17-3p reduced the blood glucose and HbAlc, increased the weight, Hb content and GS level, decreased contents of inflammatory factors and VEGF, alleviated oxidative injury, and inhibited retinal cell apoptosis in DR mice through inhibiting STAT1.

CONCLUSION

Functional studies reveal that hucMSCs-derived exosomes shuffle miR-17-3p to ameliorate inflammatory reaction and oxidative injury of DR mice via targeting STAT1.

摘要

背景

越来越多的证据表明 microRNA（miR）在糖尿病视网膜病变（DR）中发挥作用。因此，本研究旨在探讨外泌体 miR-17-3p 靶向信号转导和转录激活因子 1（STAT1）对 DR 小鼠炎症反应和抗氧化损伤的影响。

方法

建立小鼠糖尿病模型，注射含 miR-17-3p 的人脐带间充质干细胞（hucMSC）衍生的外泌体，以确定外泌体 miR-17-3p 的作用。测量 DR 小鼠血清和/或视网膜组织中的血糖、糖化血红蛋白（HbAlc）、体重、血红蛋白（Hb）含量、炎症因子、氧化应激因子、血管内皮生长因子（VEGF）、凋亡指数和谷氨酰胺合成酶（GS）水平。检测 DR 小鼠视网膜组织中 miR-17-3p 和 STAT1 的表达以及 miR-17-3p 和 STAT1 之间的靶关系。

结果

DR 小鼠视网膜组织中 miR-17-3p 减少，STAT1 增加，且 STAT1 是 miR-17-3p 的靶基因。上调的外泌体 miR-17-3p 可降低血糖和 HbAlc，增加体重、Hb 含量和 GS 水平，降低炎症因子和 VEGF 含量，减轻氧化损伤，抑制 DR 小鼠视网膜细胞凋亡，通过抑制 STAT1。