暴露于颗粒物（PM2.5）会通过下调凝血酶原-1 和紧密连接蛋白来削弱角膜防御能力。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2024-11-15 DOI:10.1016/j.ecoenv.2024.117276

Liangliang Niu , Jiamin Liu , Huan Xu , Binghui Liu , Maomao Song , Chunchun Hu , Rui Jiang , Xinghuai Sun , Yuan Lei

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引用次数: 0

摘要

背景：细颗粒物（PM2.5）通过热跃迁、氧化应激、自噬和炎症反应诱发眼表毒性。然而，PM2.5 造成角膜损伤的确切分子途径仍不清楚。本研究旨在通过将人类角膜上皮细胞（HCECs）暴露于 PM2.5 来研究其潜在机制：在对可吸入颗粒物样本进行形态和化学成分分析后，我们进行了体内和体外实验来研究PM2.5诱导的角膜上皮损伤。我们使用经皮层电阻（TEER）测定法评估了HCECs的角膜屏障功能。为了探索PM2.5诱导角膜上皮损伤的分子机制，我们在体外进行了全转录组重测序、定量RT-PCR和Western印迹。此外，我们还通过免疫荧光染色分析了暴露于高浓度环境 PM2.5 的小鼠角膜，观察角膜上皮蛋白质表达在体内的变化：结果：我们的研究结果表明，PM2.5处理的HCECs角膜上皮屏障功能明显受损，表现为TEER值下降。在体外和体内PM2.5暴露模型中，维持角膜上皮屏障完整性的两个关键因子--thrombospondin-1（THBS1）和claudin-1--在基因和蛋白水平上的表达均显著降低。此外，在经 PM2.5 处理的 HCECs 中，角膜上皮屏障的重要组成部分--紧密连接相关蛋白（包括闭塞素、闭塞带-1（ZO-1）和 ZO-2）的水平显著降低：结论：PM2.5暴露会破坏紧密连接蛋白和THBS1的表达，从而导致角膜上皮损伤。这些发现深入揭示了PM2.5诱发眼毒性的潜在途径，并强调了针对此类环境污染物采取保护策略的必要性。

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Exposure to particulate matter (PM2.5) weakens corneal defense by downregulating thrombospondin-1 and tight junction proteins

Background

Fine particulate matter (PM_2.5) induces ocular surface toxicity through pyroptosis, oxidative stress, autophagy, and inflammatory responses. However, the precise molecular pathways through which PM_2.5 causes corneal damage remain unclear. This study aims to investigate the underlying mechanisms by exposing human corneal epithelial cells (HCECs) to PM_2.5.

Methods

After the morphology and chemical composition analysis of the PM samples, we conducted both in vivo and in vitro experiments to investigate PM_2.5-induced corneal epithelial damage. We assessed corneal barrier function in HCECs using transepithelial electrical resistance (TEER) assays. To explore the molecular mechanisms of PM_2.5-induced corneal epithelial damage, we performed whole-transcriptome resequencing, quantitative RT-PCR, and western blotting in vitro. In addition, we analyzed mouse corneas exposed to concentrated ambient PM_2.5 through immunofluorescence staining to observe the resulting changes in corneal epithelial protein expression in vivo.

Results

Our results showed significant impairment of corneal epithelial barrier function in PM_2.5-treated HCECs, as indicated by decreased TEER values. The expression of thrombospondin-1 (THBS1) and claudin-1, both key factors for maintaining corneal epithelial barrier integrity, was markedly reduced at the gene and protein levels in both in vitro and in vivo PM_2.5 exposure models. Moreover, the levels of tight junction-associated proteins, including occludin, zonula occludens-1 (ZO-1) and ZO-2, essential components of the corneal epithelial barrier, were significantly diminished in PM_2.5-treated HCECs.

Conclusion

PM_2.5 exposure leads to corneal epithelium damage by disrupting tight junction proteins and THBS1 expression. These findings provide insight into potential pathways for PM_2.5-induced ocular toxicity and underscore the need for protective strategies against such environmental pollutants.

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.