Pirfenidone Ameliorates Paraquat-Induced Epithelial-Mesenchymal Transition via miR-9-8974-5p/RGS2 Axis

Irreversible and extensive pulmonary fibrosis caused by paraquat (PQ) poisoning is the main cause of death induced by PQ poisoning in developing countries. Studies have confirmed that epithelial-mesenchymal transition (EMT) contributes to the process of pulmonary interstitial fibrosis caused by PQ poisoning. Many studies have proved that a variety of miRNAs are involved in the occurrence and development of EMT. Through animal and cell experiments, we established the model of EMT on mouse lung and MLE-12 cell. We found that the expression of Regulator of G-protein signaling 2 (RGS2) was decreased in mice lung tissue and MLE-12 induced by PQ, and over-expressed/inhibited miR-9-8974-5p can decrease/increase the level of RGS2. We found that pirfenidone (PFD) can relieve PQ-induced EMT in mice lung tissue and MLE-12 cells. Meanwhile, we found that it had high expression of RGS2 in PFD group. Mimic/inhibited miR-9-8974-5p can aggravate or relieve the EMT with decreasing /increasing the level of RGS2. In conclusion, miR-9-8974-5p can mediate the pulmonary EMT induced by PQ by regulating RGS2. PFD exerts a potential therapeutic effect on PQ-induced pulmonary EMT by regulating miR-9-8974-5p/RGS2 expression.