RRC ID 68067
Author Takano M, Yamamoto C, Yamaguchi K, Kawami M, Yumoto R.
Title Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3.
Journal Drug Metab Pharmacokinet
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 effect of pirfenidone, an antifibrotic and anti-inflammatory drug, on EMT induced by TGF-β1 was also discussed.
Volume 30(1)
Pages 111-8
Published 2015-2-1
DOI 10.1016/j.dmpk.2014.10.007
PII S1347-4367(14)00016-0
PMID 25760538
MeSH ATP-Binding Cassette Transporters / genetics Actins / metabolism Animals Bleomycin / pharmacology* Cell Culture Techniques Cell Line, Tumor Epithelial Cells / drug effects* Epithelial Cells / metabolism Epithelial Cells / pathology Epithelial-Mesenchymal Transition / drug effects* Humans Keratin-19 / metabolism Methotrexate / pharmacology* Microscopy, Confocal Pulmonary Alveoli / drug effects* Pulmonary Alveoli / metabolism Pulmonary Alveoli / pathology Pyridones / pharmacology Rats Real-Time Polymerase Chain Reaction Transforming Growth Factor beta1 / pharmacology*
IF 2.772
Human and Animal Cells A549