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循环外泌体通过递送 miR-193a-5p 修复内皮细胞损伤。

Circulating exosomes repair endothelial cell damage by delivering miR-193a-5p.

机构信息

Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China.

出版信息

J Cell Mol Med. 2021 Feb;25(4):2176-2189. doi: 10.1111/jcmm.16202. Epub 2020 Dec 22.

Abstract

Circulating exosomes delivering microRNAs are involved in the occurrence and development of cardiovascular diseases. How are the circulating exosomes involved in the repair of endothelial injury in acute myocardial infarction (AMI) convalescence (3-7 days) was still not clear. In this study, circulating exosomes from AMI patients (AMI-Exo) and healthy controls (Normal-Exo) were extracted. In vitro and in vivo, our study showed that circulating exosomes protected endothelial cells (HUVECs) from oxidative stress damage; meanwhile, Normal-Exo showed better protective effects. Through the application of related inhibitors, we found that circulating exosomes shuttled between HUVECs via dynamin. Microarry analysis and qRT-PCR of circulating exosomes showed higher expression of miR-193a-5p in Normal-Exo. Our study showed that miR-193a-5p was the key factor on protecting endothelial cells in vitro and in vivo. Bioinformatics analyses found that activin A receptor type I (ACVR1) was the potential downstream target of miR-193a-5p, which was confirmed by ACVR1 expression and dual-luciferase report. Inhibitor of ACVR1 showed similar protective effects as miR-193a-5p. While overexpression of ACVR1 could attenuate protective effects of miR-193a-5p. To sum up, these findings suggest that circulating exosomes could shuttle between cells through dynamin and deliver miR-193a-5p to protect endothelial cells from oxidative stress damage via ACVR1.

摘要

循环外泌体携带的 microRNAs 参与心血管疾病的发生和发展。循环外泌体如何参与急性心肌梗死(AMI)恢复期(3-7 天)内皮损伤的修复尚不清楚。在这项研究中,从 AMI 患者(AMI-Exo)和健康对照(Normal-Exo)中提取了循环外泌体。在体外和体内,我们的研究表明循环外泌体保护内皮细胞(HUVEC)免受氧化应激损伤;同时,Normal-Exo 表现出更好的保护作用。通过应用相关抑制剂,我们发现循环外泌体通过网格蛋白在 HUVEC 之间穿梭。循环外泌体的微阵列分析和 qRT-PCR 显示 Normal-Exo 中 miR-193a-5p 的表达更高。我们的研究表明,miR-193a-5p 是体外和体内保护内皮细胞的关键因素。生物信息学分析发现激活素 A 受体 I 型(ACVR1)是 miR-193a-5p 的潜在下游靶标,这通过 ACVR1 表达和双荧光素酶报告得到证实。ACVR1 抑制剂表现出与 miR-193a-5p 相似的保护作用。而过表达 ACVR1 可减弱 miR-193a-5p 的保护作用。总之,这些发现表明,循环外泌体可以通过网格蛋白在细胞之间穿梭,并通过 ACVR1 将 miR-193a-5p 递送至内皮细胞,以保护其免受氧化应激损伤。

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