Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3

Drug Metabolism and Pharmacokinetics
Mikihisa TakanoRyoko Yumoto

Abstract

In this study, we examined the induction of epithelial-mesenchymal transition (EMT) by transforming growth factor (TGF)-β1 and drugs in genetically engineered type II alveolar epithelial cell line RLE/Abca3. Treatment of RLE/Abca3 cells with TGF-β1 induced marked changes in cell morphology from epithelial-like to elongated fibroblast-like morphology. With these morphological changes, mRNA expression of epithelial markers such as cytokeratin 19 (CK19) decreased, while that of mesenchymal markers such as α-smooth muscle actin (α-SMA) increased. TGF-β1 treatment also decreased the mRNA expression of Abca3, a type II cell marker, and formation of lamellar body structures. Interestingly, the effect of TGF-β1 on Abca3 mRNA expression was observed in RLE/Abca3 cells, but not in wild-type RLE-6TN, A549, and H441 cells. Treatment of RLE/Abca3 cells with bleomycin (BLM) and methotrexate (MTX) induced similar morphological and mRNA expression changes. In addition, the increase in α-SMA and the decrease in Abca3 mRNA expression by these drugs were observed only in RLE/Abca3 cells. These findings suggest that, like TGF-β1, BLM and MTX induce EMT in RLE/Abca3 cells, and RLE/Abca3 cells would be a good model to study drug-induced EMT. The eff...Continue Reading

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Citations

Apr 15, 2017·Journal of Pharmaceutical Sciences·Mikihisa TakanoRyoko Yumoto
Mar 28, 2018·Experimental and Therapeutic Medicine·Sang Xiong, Gong-Wei Xiao
Oct 17, 2018·The Journal of Pharmacy and Pharmacology·Masashi KawamiMikihisa Takano
Jan 7, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masashi Kawami

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