Microplastics (MPs) are plastic particles < 5 mm in diameter, of which polystyrene microplastics (PS-MPs) are representative type. The extracellular matrix (ECM) degradation of macrophages is associated with the development of emphysema. Additionally, circular RNAs (circRNAs) have a regulatory role in epigenetic mechanisms related to lung disease. However, the mechanisms of the ECM degradation and circRNAs in MPs-induced emphysema are still unclear. In our study, Sprague-Dawley (SD) rats were treated with 0, 0.5, 1.0 and 2.0 mg/m 100 nm PS-MPs for 90 days in an inhalation experiment. PS-MPs-exposed rats showed elevated airway resistance and pulmonary dysfunction. Lung histopathology exhibited inflammatory cell infiltration, septal thickening and alveolar dilatation. Exposure to PS-MPs was able to induce elevated levels of ECM degradation-related markers MMP9 and MMP12, as well as reduced levels of elastin in rat lung tissues. CircRNA_SMG6 is a non-coding RNA (ncRNA) with a homologous circular structure in human, rat and mouse. The expression level of circRNA_SMG6 was decreased in both rat lung tissues exposed to PS-MPs and PS-MPs-treated THP-1 cells. The luciferase reporter gene demonstrated that circRNA_SMG6 combined with miR-570-3p and co-regulated PTEN, the target gene of miR-570-3p. Moreover, overexpression of circRNA_SMG6 or inhibition of miR-570-3p attenuated PS-MPs-induced ECM degradation in THP-1 cells. Taken together, circRNA_SMG6 may have a significant function in the deterioration of emphysema caused by PS-MPs-induced macrophage ECM degradation by regulating miR-570-3p. Our findings reveal a novel mechanism of emphysema caused by PS-MPs and provide valuable information for assessing the health risks of MPs.

中文翻译：

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circRNA_SMG6通过miR-570-3p介导微塑料诱导肺气肿肺巨噬细胞ECM降解的机制


微塑料（MP）是直径<5毫米的塑料颗粒，其中聚苯乙烯微塑料（PS-MP）是代表性类型。巨噬细胞的细胞外基质（ECM）降解与肺气肿的发生有关。此外，环状 RNA (circRNA) 在与肺部疾病相关的表观遗传机制中具有调节作用。然而，MPs 诱导的肺气肿中 ECM 降解和 circRNA 的机制仍不清楚。在我们的研究中，Sprague-Dawley (SD) 大鼠在吸入实验中接受 0、0.5、1.0 和 2.0 mg/m 100 nm PS-MP 治疗 90 天。 PS-MPs 暴露的大鼠表现出气道阻力升高和肺功能障碍。肺组织病理学显示炎症细胞浸润、间隔增厚和肺泡扩张。暴露于 PS-MP 能够诱导 ECM 降解相关标记物 MMP9 和 MMP12 水平升高，以及大鼠肺组织中弹性蛋白水平降低。 CircRNA_SMG6 是一种在人类、大鼠和小鼠中具有同源环状结构的非编码 RNA (ncRNA)。在暴露于 PS-MP 和 PS-MP 处理的 THP-1 细胞的大鼠肺组织中，circRNA_SMG6 的表达水平均降低。荧光素酶报告基因表明circRNA_SMG6与miR-570-3p结合并共同调控miR-570-3p的靶基因PTEN。此外，circRNA_SMG6 的过表达或 miR-570-3p 的抑制减弱了 THP-1 细胞中 PS-MP 诱导的 ECM 降解。综上所述，circRNA_SMG6 可能通过调节 miR-570-3p 在 PS-MP 诱导巨噬细胞 ECM 降解引起的肺气肿恶化中发挥重要作用。我们的研究结果揭示了 PS-MP 引起肺气肿的新机制，并为评估 MP 的健康风险提供了有价值的信息。