HuMSC-EVs Protect Endothelial Cells Against Hypoxia/Reoxygenation Injury by Inhibiting the Pannexin 1/p38-MAPK Pathway

IF 0.8 4区医学 Q4 IMMUNOLOGY

Transplantation proceedings Pub Date : 2024-09-01 DOI:10.1016/j.transproceed.2024.07.007

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引用次数: 0

Abstract

Vascular endothelial cell dysfunction plays an important role in myocardial ischemia–reperfusion (I/R) injury, and pannexin 1 (Panx1), an ATP-permeable channel, is closely associated with the pathophysiological processes of I/R injury. The purpose of this study was to investigate the protective effects of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (HuMSC-EVs) and the underlying mechanism in a model of I/R injury. For the cellular model of I/R injury, human umbilical vein endothelial cells (HuVECs) were exposed to hypoxia/reoxygenation (H/R) conditions. The model cells were then treated with HuMSC-EVs, and the effects on cell survival and specific signaling activities were observed. The results showed that after H/R exposure, Panx1 expression and other markers of cellular damage were increased in HuVECs. However, treatment with HuMSC-EVs inhibited the H/R-induced increase in Panx1 expression and improved HuVEC survival. Mechanistically, HuMSC-EVs were found to inhibit the p38 mitogen-activated protein kinase (MAPK)-dependent apoptosis pathway, as evidenced by increased Bcl2 expression and reductions in p38 MAPK phosphorylation, Bax expression, and cleaved-caspase 3 expression. Together our data suggest that HuMSC-EVs alleviate H/R-induced apoptosis among HuVECs by inhibiting activity of the Panx1/p38-MAPK-dependent apoptosis pathway.

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HuMSC-EV通过抑制Pannexin 1/p38-MAPK通路保护内皮细胞免受缺氧/再氧损伤

血管内皮细胞功能障碍在心肌缺血再灌注（I/R）损伤中起着重要作用，而ATP渗透通道pannexin 1（Panx1）与I/R损伤的病理生理过程密切相关。本研究旨在探讨人脐带间充质基质细胞衍生的细胞外囊泡（HuMSC-EVs）在I/R损伤模型中的保护作用及其内在机制。在细胞I/R损伤模型中，人脐静脉内皮细胞（HuVECs）暴露于缺氧/再氧合（H/R）条件下。然后用HuMSC-EVs处理模型细胞，观察其对细胞存活和特定信号活性的影响。结果显示，H/R暴露后，HuVECs中的Panx1表达和其他细胞损伤标志物增加。然而，用HuMSC-EV处理可抑制H/R诱导的Panx1表达增加，并提高HuVEC的存活率。从机理上讲，HuMSC-EV 可抑制 p38 丝裂原活化蛋白激酶 (MAPK) 依赖性凋亡途径，表现为 Bcl2 表达增加，p38 MAPK 磷酸化、Bax 表达和裂解-天冬酶 3 表达减少。我们的数据共同表明，HuMSC-EV 通过抑制 Panx1/p38-MAPK 依赖性凋亡通路的活性，缓解了 H/R 诱导的 HuVECs 细胞凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation proceedings 医学-免疫学

CiteScore

1.70

自引率

0.00%

发文量

502

审稿时长

60 days

期刊介绍： Transplantation Proceedings publishes several different categories of manuscripts, all of which undergo extensive peer review by recognized authorities in the field prior to their acceptance for publication. The first type of manuscripts consists of sets of papers providing an in-depth expression of the current state of the art in various rapidly developing components of world transplantation biology and medicine. These manuscripts emanate from congresses of the affiliated transplantation societies, from Symposia sponsored by the Societies, as well as special Conferences and Workshops covering related topics. Transplantation Proceedings also publishes several special sections including publication of Clinical Transplantation Proceedings, being rapid original contributions of preclinical and clinical experiences. These manuscripts undergo review by members of the Editorial Board. Original basic or clinical science articles, clinical trials and case studies can be submitted to the journal?s open access companion title Transplantation Reports.