Analysis of TGF-β1- and drug-induced epithelial–mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3
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 epit...
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| Veröffentlicht in: | Drug metabolism and pharmacokinetics 2015-02, Vol.30 (1), p.111-118 |
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| creator | Takano, Mikihisa Yamamoto, Chieko Yamaguchi, Koki Kawami, Masashi Yumoto, Ryoko |
| description | 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.
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| doi_str_mv | 10.1016/j.dmpk.2014.10.007 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 1347-4367</identifier><identifier>EISSN: 1880-0920</identifier><identifier>DOI: 10.1016/j.dmpk.2014.10.007</identifier><identifier>PMID: 25760538</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Actins - metabolism ; Alveolar epithelial cells ; Animals ; ATP-Binding Cassette Transporters - genetics ; Bleomycin ; Bleomycin - pharmacology ; Cell Culture Techniques ; Cell Line, Tumor ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Epithelial-Mesenchymal Transition - drug effects ; Epithelial–mesenchymal transition ; Humans ; Keratin-19 - metabolism ; Methotrexate ; Methotrexate - pharmacology ; Microscopy, Confocal ; Pulmonary Alveoli - drug effects ; Pulmonary Alveoli - metabolism ; Pulmonary Alveoli - pathology ; Pulmonary fibrosis ; Pyridones - pharmacology ; Rats ; Real-Time Polymerase Chain Reaction ; TGF-β1 ; Transforming Growth Factor beta1 - pharmacology</subject><ispartof>Drug metabolism and pharmacokinetics, 2015-02, Vol.30 (1), p.111-118</ispartof><rights>2014 The Japanese Society for the Study of Xenobiotics</rights><rights>Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-ac3f467bd735d08b2d0dd789c62c81316bf80675bf4aa7f7689e3b313f1585e33</citedby><cites>FETCH-LOGICAL-c446t-ac3f467bd735d08b2d0dd789c62c81316bf80675bf4aa7f7689e3b313f1585e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25760538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takano, Mikihisa</creatorcontrib><creatorcontrib>Yamamoto, Chieko</creatorcontrib><creatorcontrib>Yamaguchi, Koki</creatorcontrib><creatorcontrib>Kawami, Masashi</creatorcontrib><creatorcontrib>Yumoto, Ryoko</creatorcontrib><title>Analysis of TGF-β1- and drug-induced epithelial–mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3</title><title>Drug metabolism and pharmacokinetics</title><addtitle>Drug Metab Pharmacokinet</addtitle><description>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.
[Display omitted]</description><subject>Actins - metabolism</subject><subject>Alveolar epithelial cells</subject><subject>Animals</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Bleomycin</subject><subject>Bleomycin - pharmacology</subject><subject>Cell Culture Techniques</subject><subject>Cell Line, Tumor</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Epithelial–mesenchymal transition</subject><subject>Humans</subject><subject>Keratin-19 - metabolism</subject><subject>Methotrexate</subject><subject>Methotrexate - pharmacology</subject><subject>Microscopy, Confocal</subject><subject>Pulmonary Alveoli - drug effects</subject><subject>Pulmonary Alveoli - metabolism</subject><subject>Pulmonary Alveoli - pathology</subject><subject>Pulmonary fibrosis</subject><subject>Pyridones - pharmacology</subject><subject>Rats</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>TGF-β1</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><issn>1347-4367</issn><issn>1880-0920</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtq3DAUhkVJaG59gSyKltl4Ilm2pIFuhpAbDARCshaydNxoKstTyQ7MotB36Jv0QfIQeZLITBKyyuqIw_f_HH0IHVMyo4Ty09XMdutfs5LQKi9mhIgvaJ9KSQoyL8lOfrNKFBXjYg8dpLQihLG6Kr-ivbIWnNRM7qM_i6D9JrmE-xbfXV4UT_9pgXWw2MbxZ-GCHQ1YDGs3PIB32j___ddBgmAeNp32eIg6JDe4PmAXsBn9MMbMa_8IvdfxQxAb8B57FwDfLs9PF43R7Ajttton-PY6D9H9xfnd2VWxvLm8PlssC1NVfCi0YW3FRWMFqy2RTWmJtULODS-NpIzyppWEi7ppK61FK7icA2sYZS2tZQ2MHaKTbe869r9HSIPqXJru0QH6MSnKOeM156XIaLlFTexTitCqdXSdjhtFiZq0q5WatKtJ-7TL2nPo-2v_2HRg3yNvnjPwYwtA_uWjg6iScVkiWBfBDMr27rP-F058lfc</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Takano, Mikihisa</creator><creator>Yamamoto, Chieko</creator><creator>Yamaguchi, Koki</creator><creator>Kawami, Masashi</creator><creator>Yumoto, Ryoko</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150201</creationdate><title>Analysis of TGF-β1- and drug-induced epithelial–mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3</title><author>Takano, Mikihisa ; Yamamoto, Chieko ; Yamaguchi, Koki ; Kawami, Masashi ; Yumoto, Ryoko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-ac3f467bd735d08b2d0dd789c62c81316bf80675bf4aa7f7689e3b313f1585e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Actins - metabolism</topic><topic>Alveolar epithelial cells</topic><topic>Animals</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>Bleomycin</topic><topic>Bleomycin - pharmacology</topic><topic>Cell Culture Techniques</topic><topic>Cell Line, Tumor</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Epithelial–mesenchymal transition</topic><topic>Humans</topic><topic>Keratin-19 - metabolism</topic><topic>Methotrexate</topic><topic>Methotrexate - pharmacology</topic><topic>Microscopy, Confocal</topic><topic>Pulmonary Alveoli - drug effects</topic><topic>Pulmonary Alveoli - metabolism</topic><topic>Pulmonary Alveoli - pathology</topic><topic>Pulmonary fibrosis</topic><topic>Pyridones - pharmacology</topic><topic>Rats</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>TGF-β1</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takano, Mikihisa</creatorcontrib><creatorcontrib>Yamamoto, Chieko</creatorcontrib><creatorcontrib>Yamaguchi, Koki</creatorcontrib><creatorcontrib>Kawami, Masashi</creatorcontrib><creatorcontrib>Yumoto, Ryoko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Drug metabolism and pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takano, Mikihisa</au><au>Yamamoto, Chieko</au><au>Yamaguchi, Koki</au><au>Kawami, Masashi</au><au>Yumoto, Ryoko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of TGF-β1- and drug-induced epithelial–mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3</atitle><jtitle>Drug metabolism and pharmacokinetics</jtitle><addtitle>Drug Metab Pharmacokinet</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>30</volume><issue>1</issue><spage>111</spage><epage>118</epage><pages>111-118</pages><issn>1347-4367</issn><eissn>1880-0920</eissn><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.
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| subjects | Actins - metabolism Alveolar epithelial cells Animals ATP-Binding Cassette Transporters - genetics Bleomycin Bleomycin - pharmacology Cell Culture Techniques Cell Line, Tumor Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial Cells - pathology Epithelial-Mesenchymal Transition - drug effects Epithelial–mesenchymal transition Humans Keratin-19 - metabolism Methotrexate Methotrexate - pharmacology Microscopy, Confocal Pulmonary Alveoli - drug effects Pulmonary Alveoli - metabolism Pulmonary Alveoli - pathology Pulmonary fibrosis Pyridones - pharmacology Rats Real-Time Polymerase Chain Reaction TGF-β1 Transforming Growth Factor beta1 - pharmacology |
| title | Analysis of TGF-β1- and drug-induced epithelial–mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3 |
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