College of Medical Laboratory, Dalian Medical University, Dalian, 116044, Liaoning Province, China; Department of Clincal Laboratory, The Fourth People's Hospital of Shenyang, Shenyang, 110031, Liaoning Province, China.
Department of Neurosurgery, Dalian Central Hospital, Dalian, 116033, Liaoning Province, China.
Ecotoxicol Environ Saf. 2020 Dec 1;205:111327. doi: 10.1016/j.ecoenv.2020.111327. Epub 2020 Sep 19.
Exposure to PM can cause serious harm to the respiratory system. Until now, although many toxicological studies have shown that pulmonary fibrosis can be caused by long-term PM exposure, there is no evidence that Endothelial-Mesenchymal Transition (EndMT) can trigger the process of pulmonary fibrosis after exposure. LncRNAs are a class of non-coding RNAs detected in mammalian cells. Nevertheless, researchers have not found whether lncRNAs participate in PM induced EndMT during pathophysiological duration. The Balb/c mouse model was exposed to PM for 4 months by dynamic intoxication. The levels of specific endothelial and mesenchymal markers were evaluated by molecular biology experiments to elucidate the mechanisms of EndMT induced by PM in lung tissues. LncRNA microarray analysis of the established mouse model of PM exposure was performed. Based on a bioinformatics analysis and RT-qPCR analysis, lncRNA Gm16410 attracted our attention. The change of lncRNA Gm16410 in mouse pulmonary vascular endothelial cells (MHCs) exposed to PM was verified, and the mechanism of lncRNA Gm16410 in EndMT was discussed. The changes of cell function were evaluated by cell migration and proliferation experiments. The molecular biology experiments proved that PM induced EndMT by activating the TGF-β1/Smad3/p-Smad3 pathway in vitro. The relationship of EndMT and lncRNA Gm16410 was verified in mouse lung tissues and MHC cells by PM exposure. The involvement of lncRNA Gm16410 in PM-induced EndMT highlights the potential of lncRNA to promote pulmonary fibrosis under environmental pollution.
PM 暴露可对呼吸系统造成严重损害。迄今为止，尽管许多毒理学研究表明，长期 PM 暴露可导致肺纤维化，但尚无证据表明内皮-间充质转化（EndMT）可引发暴露后的肺纤维化过程。LncRNAs 是在哺乳动物细胞中检测到的一类非编码 RNA。然而，研究人员尚未发现长链非编码 RNA 是否在生理病理期间参与 PM 诱导的 EndMT。Balb/c 小鼠模型通过动态染毒暴露于 PM 4 个月。通过分子生物学实验评估特定的内皮和间充质标志物的水平，以阐明 PM 在肺组织中诱导 EndMT 的机制。对建立的 PM 暴露小鼠模型进行 lncRNA 微阵列分析。基于生物信息学分析和 RT-qPCR 分析，长链非编码 RNA Gm16410 引起了我们的关注。验证了 PM 暴露的小鼠肺血管内皮细胞（MHCs）中长链非编码 RNA Gm16410 的变化，并讨论了长链非编码 RNA Gm16410 在 EndMT 中的作用机制。通过细胞迁移和增殖实验评估细胞功能变化。分子生物学实验证明 PM 通过激活 TGF-β1/Smad3/p-Smad3 通路在体外诱导 EndMT。通过 PM 暴露在小鼠肺组织和 MHC 细胞中验证了 EndMT 与长链非编码 RNA Gm16410 的关系。长链非编码 RNA Gm16410 参与 PM 诱导的 EndMT 强调了长链非编码 RNA 在环境污染下促进肺纤维化的潜力。
