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

Abstract

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.