Paraquat poisoning induced pulmonary epithelial mesenchymal transition through Notch1 pathway

Abstract

Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch signaling is required for EMT. In this study, we investigated whether Notch1 and TGF-β1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated that A549 cells underwent EMT after treated with PQ at dose of 300 μmol/L for 6 days, charactered by increasing expression of mesenchymal marker α-SMA and decreasing expression of epithelial marker E-cadherin. We found that there was an apparent increased expression of Notch1 and jagged-1 in PQ induced EMT process. EMT could be enhanced by Jagged-1 ligand of Notch1, and be blocked by DAPT, a 3-secretase inhibitor. Our data also showed that the expression of TGF-β1/Smad3 increased after Notch1 is elevated in EMT caused by PQ. Jagged-1 significantly induced SMA expression, and this induction was completely inhibited by SB431542 in A549 cells. In conclusion, we demonstrated that Notch1 pathway was important in EMT induced by PQ, and TGF-β1/Smad3 signaling partly plays a role as the downstream of Notch1.