Analysis of TGF-beta 1-and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3

作者：Takano, Mikihisa^*; Yamamoto, Chieko; Yamaguchi, Koki; Kawami, Masashi; Yumoto, Ryoko

来源：Drug Metabolism and Pharmacokinetics, 2015, 30(1): 111-118.

DOI：10.1016/j.dmpk.2014.10.007

• Pulmonary fibrosis
• Alveolar epithelial cells
• TGF-beta 1
• Bleomycin
• Methotrexate
• Epithelial-mesenchymal transition

In this study, we examined the induction of epithelial-mesenchymal transition (EMT) by transforming growth factor (TGF)-beta 1 and drugs in genetically engineered type II alveolar epithelial cell line RLE/Abca3. Treatment of RLE/Abca3 cells with TGF-beta 1 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 alpha-smooth muscle actin (alpha-SMA) increased. TGF-beta 1 treatment also decreased the mRNA expression of Abca3, a type II cell marker, and formation of lamellar body structures. Interestingly, the effect of TGF-beta 1 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 alpha-SMA and the decrease in Abca3 mRNA expression by these drugs were observed only in RLE/Abca3 cells. These findings suggest that, like TGF-beta 1, 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-beta 1 was also discussed.

• 出版日期2015-2