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Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3.
Drug Metab Pharmacokinet. 2015 Feb; 30(1):111-8.DM

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.

Authors+Show Affiliations

Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Electronic address: takanom@hiroshima-u.ac.jp.Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25760538

Citation

Takano, Mikihisa, et al. "Analysis of TGF-β1- and Drug-induced Epithelial-mesenchymal Transition in Cultured Alveolar Epithelial Cell Line RLE/Abca3." Drug Metabolism and Pharmacokinetics, vol. 30, no. 1, 2015, pp. 111-8.
Takano M, Yamamoto C, Yamaguchi K, et al. Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3. Drug Metab Pharmacokinet. 2015;30(1):111-8.
Takano, M., Yamamoto, C., Yamaguchi, K., Kawami, M., & Yumoto, R. (2015). Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3. Drug Metabolism and Pharmacokinetics, 30(1), 111-8. https://doi.org/10.1016/j.dmpk.2014.10.007
Takano M, et al. Analysis of TGF-β1- and Drug-induced Epithelial-mesenchymal Transition in Cultured Alveolar Epithelial Cell Line RLE/Abca3. Drug Metab Pharmacokinet. 2015;30(1):111-8. PubMed PMID: 25760538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3. AU - Takano,Mikihisa, AU - Yamamoto,Chieko, AU - Yamaguchi,Koki, AU - Kawami,Masashi, AU - Yumoto,Ryoko, Y1 - 2014/11/04/ PY - 2014/06/13/received PY - 2014/09/06/revised PY - 2014/10/13/accepted PY - 2015/3/12/entrez PY - 2015/3/12/pubmed PY - 2016/3/22/medline KW - Alveolar epithelial cells KW - Bleomycin KW - Epithelial–mesenchymal transition KW - Methotrexate KW - Pulmonary fibrosis KW - TGF-β1 SP - 111 EP - 8 JF - Drug metabolism and pharmacokinetics JO - Drug Metab Pharmacokinet VL - 30 IS - 1 N2 - 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. SN - 1880-0920 UR - https://www.unboundmedicine.com/medline/citation/25760538/Analysis_of_TGF_β1__and_drug_induced_epithelial_mesenchymal_transition_in_cultured_alveolar_epithelial_cell_line_RLE/Abca3_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1347-4367(14)00016-0 DB - PRIME DP - Unbound Medicine ER -