LncRNA Gm16410 regulates PM2.5-induced lung Endothelial-Mesenchymal Transition via the TGF-β1/Smad3/p-Smad3 pathway

Abstract

Exposure to PM_2.5 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_2.5 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_2.5 induced EndMT during pathophysiological duration. The Balb/c mouse model was exposed to PM_2.5 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_2.5 in lung tissues. LncRNA microarray analysis of the established mouse model of PM_2.5 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_2.5 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_2.5 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_2.5 exposure. The involvement of lncRNA Gm16410 in PM_2.5-induced EndMT highlights the potential of lncRNA to promote pulmonary fibrosis under environmental pollution.