Suppressive effect of quercetin against bleomycin-induced epithelial-mesenchymal transition in alveolar epithelial cells
Suppressive effect of quercetin against bleomycin-induced epithelial-mesenchymal transition in alveolar epithelial cells
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DOI：
10.1016/j.dmpk.2020.08.001
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发表时间：
2020-12-01
影响因子：
2.1
通讯作者：
Yumoto, Ryoko
中科院分区：
文献类型：
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作者：
Takano, Mikihisa;Deguchi, Junya;Yumoto, Ryoko
槲皮素是一种黄酮醇，已知具有许多有益的生物效应，例如抗纤维化作用。肺泡II型上皮细胞的上皮间质转化（EMT）是肺纤维化的主要原因之一。然而，槲皮素对药物诱导的 II 型肺泡细胞 EMT 的影响尚不清楚。在这项研究中，我们使用具有肺泡 II 型细胞样表型的 RLE/Abca3 细胞检查了槲皮素对博来霉素 (BLM) 诱导的 EMT 的影响。 BLM 诱导 RLE/Abca3 细胞中类似 EMT 的形态变化、上皮标记物 E-钙粘蛋白的下调以及间充质标记物 α-平滑肌肌动蛋白的上调。此外，BLM 增加了磷酸化 Smad2 和 Slug mRNA 表达水平，并增强了 β-catenin 的核转位，表明 BLM 通过 Smad 和 β-catenin 信号通路诱导 RLE/Abca3 细胞中的 EMT。然而，当细胞与槲皮素共同处理时，槲皮素抑制了 BLM 诱导的所有这些 EMT 相关变化。此外，BLM 增加了细胞内活性氧的水平，而槲皮素也抑制了活性氧的水平。这些结果表明槲皮素可能是预防药物引起的肺纤维化的候选药物。 (C) 2020 年由 Elsevier Ltd 代表日本异生素研究会出版。
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.