MiR-421通过支气管上皮细胞和内皮细胞之间的串扰介导PM2.5诱导的内皮功能障碍。

IF 2 4区 医学 Q4 TOXICOLOGY
Inhalation Toxicology Pub Date : 2024-10-01 Epub Date: 2024-05-22 DOI:10.1080/08958378.2024.2356839
Yiqing Chen, Mengting Zeng, Jinxin Xie, Zhihao Xiong, Yuxin Jin, Zihan Pan, Michail Spanos, Tianhui Wang, Hongyun Wang
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引用次数: 0

摘要

目的:PM2.5 与血管内皮损伤密切相关,已成为人类健康的主要威胁。我们之前的研究表明,暴露于 PM2.5 会诱导支气管上皮细胞释放更多的 miR-421。然而,miR-421在PM2.5诱导的内皮损伤中的作用仍不明确:我们利用体内亚急性 PM2.5 暴露小鼠模型和体外急性损伤细胞模型模拟 PM2.5 相关的内皮损伤。我们还使用了定量实时聚合酶链反应、Western 印迹、酶联免疫吸附试验和免疫组织化学方法来研究 miR-421 在 PM2.5 诱导的内皮损伤中的作用:结果:我们的研究结果表明,抑制 miR-421 可减轻 PM2.5 诱导的内皮损伤和高血压。从机制上讲,miR-421 可抑制血管紧张素转换酶 2(ACE2)在人脐静脉内皮细胞中的表达,并上调下游分子诱导型一氧化氮合酶(iNOS)的表达,从而加剧 PM2.5 诱导的内皮损伤:我们的研究结果表明,PM2.5 暴露通过 miR-421/ACE2/iNOS 信号通路促进支气管上皮细胞和内皮细胞之间的串扰,介导内皮损伤和高血压。抑制 MiR-421 可为预防和治疗 PM2.5 诱导的血管内皮损伤提供一种新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MiR-421 mediates PM2.5-induced endothelial dysfunction via crosstalk between bronchial epithelial and endothelial cells.

Objective: PM2.5 is closely linked to vascular endothelial injury and has emerged as a major threat to human health. Our previous research indicated that exposure to PM2.5 induced an increased release of miR-421 from the bronchial epithelium. However, the role of miR-421 in PM2.5-induced endothelial injury remains elusive.

Materials and methods: We utilized a subacute PM2.5-exposure model in mice in vivo and an acute injury cell model in vitro to simulate PM2.5-associated endothelial injury. We also used quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry to investigate the role of miR-421 in PM2.5-induced endothelial injury.

Results: Our findings reveal that inhibition of miR-421 attenuated PM2.5-induced endothelial injury and hypertension. Mechanistically, miR-421 inhibited the expression of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein endothelial cells and upregulated the expression of the downstream molecule inducible nitric oxide synthase (iNOS), thereby exacerbating PM2.5-induced endothelial injury.

Conclusions: Our results indicate that PM2.5 exposure facilitates crosstalk between bronchial epithelial and endothelial cells via miR-421/ACE2/iNOS signaling pathway, mediating endothelial damage and hypertension. MiR-421 inhibition may offer a new strategy for the prevention and treatment of PM2.5-induced vascular endothelial injury.

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来源期刊
Inhalation Toxicology
Inhalation Toxicology 医学-毒理学
CiteScore
4.10
自引率
4.80%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Inhalation Toxicology is a peer-reviewed publication providing a key forum for the latest accomplishments and advancements in concepts, approaches, and procedures presently being used to evaluate the health risk associated with airborne chemicals. The journal publishes original research, reviews, symposia, and workshop topics involving the respiratory system’s functions in health and disease, the pathogenesis and mechanism of injury, the extrapolation of animal data to humans, the effects of inhaled substances on extra-pulmonary systems, as well as reliable and innovative models for predicting human disease.
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