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氧化诱导的血管生成受视网膜色素上皮细胞中小细胞外囊泡miR-302a-3p货物的调节。

Oxidative-Induced Angiogenesis Is Modulated by Small Extracellular Vesicle miR-302a-3p Cargo in Retinal Pigment Epithelium Cells.

作者信息

Oltra Maria, Martínez-Santos Miriam, Ybarra María, Rowland Hugo, Muriach María, Romero Javier, Sancho-Pelluz Javier, Barcia Jorge M

机构信息

Neurophysiology and Neurobiology, School of Medicine and Health Sciences, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain.

Centro de Investigación Translacional San Alberto Magno, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain.

出版信息

Antioxidants (Basel). 2022 Apr 22;11(5):818. doi: 10.3390/antiox11050818.

DOI:10.3390/antiox11050818
PMID:35624680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9137950/
Abstract

Extracellular vesicles are released from cells under diverse conditions. Widely studied in cancer, they are associated with different diseases playing major roles. Recent reports indicate that oxidative damage promotes the release of small extracellular vesicle (sEVs) from the retinal pigment epithelium (RPE), with an angiogenic outcome and changes in micro-RNA (miRNA) levels. The aim of this study was to determine the role of the miRNA miR-302a-3p, included within RPE-released sEVs, as an angiogenic regulator in cultures of endothelial cells (HUVEC). ARPE-19 cell cultures, treated with HO to cause an oxidative insult, were transfected with a miR-302a-3p . Later, sEVs from the medium were isolated and added into HUVEC or ARPE-19 cultures. sEVs from ARPE-19 cells under oxidative damage presented a decrease of miR-302a-3p levels and exhibited proangiogenic properties. In contrast, sEVs from miR-302a-3p- transfected cells resulted in control angiogenic levels. The results herein indicate that miR-302a-3p contained in sEVs can modify VEGFA mRNA expression levels as part of its antiangiogenic features.

摘要

细胞外囊泡在多种条件下从细胞中释放出来。它们在癌症研究中得到广泛关注,与不同疾病相关并发挥着重要作用。最近的报告表明,氧化损伤会促进视网膜色素上皮(RPE)释放小细胞外囊泡(sEVs),并产生血管生成结果以及微小RNA(miRNA)水平的变化。本研究的目的是确定RPE释放的sEVs中所含的miRNA miR - 302a - 3p在内皮细胞(HUVEC)培养物中作为血管生成调节因子的作用。用HO处理ARPE - 19细胞培养物以造成氧化损伤,然后用miR - 302a - 3p进行转染。随后,从培养基中分离出sEVs,并将其添加到HUVEC或ARPE - 19培养物中。氧化损伤条件下ARPE - 19细胞的sEVs中miR - 302a - 3p水平降低,并表现出促血管生成特性。相比之下,来自miR - 302a - 3p转染细胞的sEVs导致血管生成水平处于对照状态。本文结果表明,sEVs中所含的miR - 302a - 3p可作为其抗血管生成特性的一部分,改变VEGFA mRNA的表达水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24cf/9137950/8d93f231be17/antioxidants-11-00818-g008.jpg
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