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

• Published in: Drug metabolism and pharmacokinetics 2020-12, Vol.35 (6), p.522-526
• Main Authors: Takano, Mikihisa, Deguchi, Junya, Senoo, Shunsuke, Izumi, Miho, Kawami, Masashi, Yumoto, Ryoko
• Format: Article
• Language: English
• Subjects: Alveolar epithelial cells; Bleomycin; Epithelial-mesenchymal transition; Quercetin
• ISSN: 1347-4367; 1880-0920
• DOI: 10.1016/j.dmpk.2020.08.001

Quercetin is a flavonol that is known to have numerous beneficial biological effects such as an anti-fibrotic 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 α-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 β-catenin, suggesting that BLM induced EMT in RLE/Abca3 cells via Smad and β-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. [Display omitted]