Effect of COA-Cl on transforming growth factor-β1-induced epithelial–mesenchymal transition in RLE/Abca3 cells. Issue 4 (August 2017)

• Record Type: Journal Article
• Authors: Kawami, Masashi; Deguchi, Junya; Yumoto, Ryoko; Sakakibara, Norikazu; Tsukamoto, Ikuko; Konishi, Ryoji; Takano, Mikihisa
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 32:Issue 4(2017)
• Page Start: 224
• Page End: 227
• Publication Date: 2017-08
• Subjects: Alveolar epithelial cells -- COA-Cl -- Epithelial–mesenchymal transition -- Snail -- Transforming growth factor-β1 -- ZEB; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2017.05.001
• Languages: English
• ISSNs: 1347-4367

Abstract

Abstract: Transforming growth factor (TGF)-β1 has received much attention as a major inducer of epithelial–mesenchymal transition (EMT) in pathological conditions such as cancer and organ fibrosis. In this study, we examined the effect of a novel nucleic acid analog, COA-Cl, on TGF-β1-induced EMT using RLE/Abca3, a cell line having alveolar type II cell-like phenotype. Changes in the cell morphology consistent with EMT were induced by TGF-β1, whereas, this response was suppressed by co-treatment of the cells with COA-Cl. In addition, co-treatment with COA-Cl abolished TGF-β1-induced downregulation of cytokeratin 19 and upregulation of α-smooth muscle actin transcripts. In order to delineate the mechanism underlying the inhibitory effect of COA-Cl on TGF-β1-induced EMT in RLE/Abca3 cells, we examined the role of zinc finger E-box binding homeobox (ZEB) family transcription factors in this phenomenon. Our results demonstrated that the treatment of cells with COA-Cl suppressed the TGF-β1 mediated increase in the mRNA levels of ZEB2. Overall, it was concluded that COA-Cl may have an inhibitory effect on TGF-β1-induced EMT-like phenotypical changes in RLE/Abca3 cells via suppression of ZEB2 mRNA expression. Graphical abstract: