Suppressive effect of quercetin against bleomycin-induced epithelial-mesenchymal transition in alveolar epithelial cells

Quercetin is a flavonol that is known to have numerous beneficial biological effects such as an antifibrotic effect. Epithelial-mesenchymal transition (EMT) of alveolar type II epithelial cells is one of major causes of pulmonary fibrosis. However, the effect of quercetin on drug-induced EMT in alveolar type II cells is not known. In this study, we examined the effect of quercetin on bleomycin (BLM)-induced EMT using RLE/Abca3 cells having alveolar type II cell-like phenotype. BLM induced EMT-like morphological changes, downregulation of an epithelial marker E-cadherin, and upregulation of a mesenchymal marker alpha-smooth muscle actin in RLE/Abca3 cells. In addition, BLM increased the levels of phosphorylated Smad2 and Slug mRNA expression, and enhanced nuclear translocation of beta-catenin, suggesting that BLM induced EMT in RLE/Abca3 cells via Smad and beta-catenin signaling pathways. However, when the cells were co-treated with quercetin, quercetin suppressed all of these EMT-related changes induced by BLM. Furthermore, BLM increased the intracellular level of reactive oxygen species, which was also suppressed by quercetin. These results suggest that quercetin may be a possible candidate for preventing pulmonary fibrosis caused by drugs. (C) 2020 Published by Elsevier Ltd on behalf of The Japanese Society for the Study of Xenobiotics.