Department of Emergency, The First Affiliated Hospital of China Medical University, China.
J Toxicol Sci. 2020;45(8):423-434. doi: 10.2131/jts.45.423.
Paraquat (PQ) as a non-selective heterocyclic herbicide, has been applied worldwide for over a few decades. But PQ is very harmful to humans and rodents. The lung is the main target organ of PQ poisoning. It is an important event that lung epithelial cells are injured during PQ-induced acute lung injury and pulmonary fibrosis. As a regulator of mRNA expression, microRNA (miRNA) may play an important role in the progress. Our study was to investigate the mechanisms of PQ-induced injury of pulmonary epithelial cells through analyzing the profiling of miRNAs and their target genes. As a result, 11 differentially expressed miRNAs were screened, including 1 upregulated miRNA and 10 downregulated miRNAs in PQ-treated murine lung alveolar epithelial cells (MLE-12 cells). The bioinformatic analyses suggested that the target genes of these miRNAs were involved in mitochondrial apoptosis pathway and DNA methylation, and participated in the regulation of PI3K-Akt, mTOR, RAS, TNF, MAPK and other signal pathways which related to oxidative stress and apoptosis. This indicated that miRNAs were an important regulator of oxidative stress and apoptosis during PQ-induced injury of murine lung alveolar epithelial cells. The findings would deepen our understanding of the mechanisms of PQ-induced pulmonary injury and might provide new treatment targets for this disease.
百草枯（PQ）作为一种非选择性杂环类除草剂，在全球范围内已经应用了几十年。但 PQ 对人类和啮齿动物有很大的危害。肺是 PQ 中毒的主要靶器官。PQ 诱导的急性肺损伤和肺纤维化过程中肺上皮细胞损伤是一个重要事件。作为 mRNA 表达的调节剂，microRNA（miRNA）可能在进展中发挥重要作用。我们的研究通过分析 miRNA 及其靶基因的谱，来探讨 PQ 诱导的肺上皮细胞损伤的机制。结果筛选出 11 个差异表达的 miRNA，包括 PQ 处理的鼠肺泡上皮细胞（MLE-12 细胞）中 1 个上调的 miRNA 和 10 个下调的 miRNA。生物信息学分析表明，这些 miRNA 的靶基因参与线粒体凋亡途径和 DNA 甲基化，并参与调节与氧化应激和凋亡相关的 PI3K-Akt、mTOR、RAS、TNF、MAPK 等信号通路。这表明 miRNA 是 PQ 诱导的鼠肺肺泡上皮细胞损伤过程中氧化应激和凋亡的重要调节因子。这些发现将加深我们对 PQ 诱导的肺损伤机制的理解，并可能为该疾病提供新的治疗靶点。
