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PM2.5 导致肺损伤中的 microRNA 失调和炎症微环境。

PM2.5 deregulated microRNA and inflammatory microenvironment in lung injury.

机构信息

Department of Pathogen Biology, Shenyang Medical College, No. 146, Huanghe North Street, Shenyang, People's Republic of China.

Department of Respiratory Medicine, Affiliated Center Hospital of Shenyang Medical College, No. 5, Nanqi West Road, Shenyang, People's Republic of China.

出版信息

Environ Toxicol Pharmacol. 2022 Apr;91:103832. doi: 10.1016/j.etap.2022.103832. Epub 2022 Feb 19.

Abstract

PM2.5 negatively affects human health, particularly lung injury. However, the role of PM2.5-regulated miRNAs in lung injury remains unknown. MiRNA array results showed mmu-miR-467c-5p regulated Prdx6 expression to adapt to lung injury condition, and deregulated miRNAs regulated macrophages to build a localized inflammatory microenvironment. In addition, miRNAs were transferred into adjacent alveolar epithelial cells, regulating the expressions of cell injury signaling pathway-targeted genes, and accelerating local lung tissue injury. NO and RAGE were increased in the coculture supernatant, and SPD was decreased. PM2.5 exposure induced local lung injury, promoted inflammation in local lung tissues, increased capillary permeability in the lung tissue, and rearranged the local lung tissue structure. We also confirmed in AECOPD patients TNF-α and IL-1β levels are obviously higher than healthy person. These findings provide new mechanistic insights regarding PM2.5 and targeted miRNAs in the inflammatory microenvironment, which increases our knowledge of PM2.5-lung injury interactions.

摘要

PM2.5 会对人体健康造成负面影响,特别是肺部损伤。然而,PM2.5 调节的 miRNA 在肺部损伤中的作用仍不清楚。miRNA 芯片结果表明,mmu-miR-467c-5p 通过调节 Prdx6 的表达来适应肺部损伤的情况,而失调的 miRNA 则调节巨噬细胞来构建局部炎症微环境。此外,miRNA 被转移到相邻的肺泡上皮细胞中,调节细胞损伤信号通路靶向基因的表达,从而加速局部肺组织损伤。共培养上清液中 NO 和 RAGE 增加,SPD 减少。PM2.5 暴露会导致局部肺损伤,促进局部肺组织炎症,增加肺组织毛细血管通透性,并重新排列局部肺组织结构。我们还在 AECOPD 患者中证实 TNF-α 和 IL-1β 的水平明显高于健康人。这些发现为 PM2.5 和炎症微环境中的靶向 miRNA 提供了新的机制见解,增加了我们对 PM2.5-肺部损伤相互作用的认识。

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