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Effects of dexamethasone on the TGF-β1-induced epithelial-to- mesenchymal transition in human peritoneal mesothelial cells

Title
Effects of dexamethasone on the TGF-β1-induced epithelial-to- mesenchymal transition in human peritoneal mesothelial cells
Authors
Jang Y.-H.Shin H.-S.Sun Choi H.Ryu E.-S.Jin Kim M.Ki Min S.Lee J.-H.Kook Lee H.Kim K.-H.Kang D.-H.
Ewha Authors
강덕희김광호이주호이현국민석기최학선
SCOPUS Author ID
강덕희scopus; 김광호scopus; 이주호scopus; 이현국scopus; 민석기scopus
Issue Date
2013
Journal Title
Laboratory Investigation
ISSN
0023-6837JCR Link
Citation
vol. 93, no. 2, pp. 194 - 206
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The epithelial-to-mesenchymal transition (EMT) is known to have a role in appropriate embryonic development, the physiological response to injury and pathological events such as organ fibrosis and cancer progression. Glucocorticoid (GC), one of the most commonly used anti-inflammatory drugs, inhibits the deposition of extracellular matrix independent of its anti-inflammatory effect. The EMT of human peritoneal mesothelial cells (HPMCs) is a key mechanism of peritoneal fibrosis; however, it has not yet been investigated whether GC imposes any effect on the EMT of HPMCs. To investigate the therapeutic potential of GC on preserving peritoneal membrane function, we studied the effect of dexamethasone (DEXA), a synthetic GC, on the transforming growth factor-β1 (TGF-β1)-induced EMT in HPMCs. As assessed by changes in cell morphology, the expression of epithelial and mesenchymal cell markers (such as E-cadherin, ZO-1 and α-SMA, α-smooth muscle actin) and cell migration, DEXA inhibited the TGF-β1-induced EMT. RU486, a glucocorticoid receptor (GR) antagonist, blocked the effect of DEXA on the TGF-β1-induced EMT. Importantly, DEXA also induced the mesenchymal-to-epithelial transition of TGF-β1-stimulated HPMCs. The beneficial effect of DEXA on the TGF-β1-induced EMT was mediated through the amelioration of ERK and p38 mitogen-activated protein kinase (MAPK) phosphorylation; however, this effect was not related to the TGF-β1-induced activation of Smad2/3 signaling. DEXA inhibited glycogen synthase kinase-3β (GSK-3β) phosphorylation and the Snail upregulation induced by TGF-β1, which were also ameliorated by inhibitors of MAPK. In conclusion, this is the first study demonstrating the protective effect of DEXA on the EMT in TGF-β1-stimulated HPMCs by inhibiting MAPK activation, GSK-3β phosphorylation and Snail upregulation. © 2013 USCAP, Inc All rights reserved.
DOI
10.1038/labinvest.2012.166
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의과대학 > 의학과 > Journal papers
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