Glucocorticoid induces mesenchymal-to-epithelial transition and inhibits TGF-β1-induced epithelial-to-mesenchymal transition and cell migration.
Epithelial-to-mesenchymal transition (EMT) has been implicated in various physiological and pathological events. In this study, we found that the synthetic glucocorticoid dexamethasone (Dex) can inhibit transforming growth factor-beta1-induced EMT and cell migration. We also demonstrated that Dex inhibits EMT through a mechanism involving the suppression of ROS generation. Surprisingly, Dex alone induced mesenchymal-to-epithelial transition (MET). Dexamethasone treatment abolished Snail1 binding to the E-cadherin promoter, suggesting that suppression of Snail1 contributes to the above roles of Dex. Our findings demonstrate that Dex functions as both a suppressor of EMT and as an inducer of MET and therefore may be implicated in certain pathophysiological events.
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. 320 Yue-Yang Road, Shanghai 200031, China.
Liang
L
Zhang
Weiwei
W
Lei
Xunde
X
Wang
Yunneng
Y
Tang
Jianguo
J
Song
D015820:Cadherins / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D015820:Cadherins; D017382:Reactive Oxygen Species; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D015735:Mifepristone; D003907:Dexamethasone