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

Yang Hee Jang, Hyun Soo Shin, Hack Sun Choi, Eun Sun Ryu, Mi Jin Kim, Seog Ki Min, Joo Ho Lee, Hyeon Kook Lee, Kwang Ho Kim, Duk Hee Kang

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


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.

Original languageEnglish
Pages (from-to)194-206
Number of pages13
JournalLaboratory Investigation
Issue number2
StatePublished - Feb 2013

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (A100422).


  • TGF-β
  • dexamethasone
  • epithelial-to-mesenchymal transition
  • human peritoneal mesothelial cells
  • peritoneal fibrosis


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