Prostaglandin D2 inhibits TGF-β1-induced epithelial-to-mesenchymal transition in MDCK cells

Aihua Zhang, Zheng Dong, Tianxin Yang

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

In a separate study, we identified PGE2 as a potent inhibitor of TGF-β1-induced epithelial-mesenchymal transition (EMT) in cultured Madin-Darby canine kidney (MDCK) cells (Zhang A, Wang M-H, Dong Z, and Yang T. Am J Physiol Renal Physiol 291: F1323-F1331, 2006). This finding prompted us to examine the roles of other prostanoids: PGD2, PGF , PGI2, and thromboxane A2 (TXA 2). Treatment with 10 ng/ml TGF-β1 for 3 days induced EMT as reflected by conversion to the spindle-like morphology, loss of E-cadherin, and activation of α-smooth muscle actin (α-SMA). Treatment with PGD2 remarkably preserved the epithelial-like morphology, restored the expression of E-cadherin, and abolished the activation of α-SMA. In contrast, PGF, carbocyclic thromboxane A2, PGI2 and its stable analog beraprost were without an effect. MDCK cells expressed DP1 and DP2 receptors; however, the effect of PGD2 was neither prevented by DP1 antagonist BW-A868C or DP2 antagonist BAY-u3405 nor was mimicked by DP1 agonist BW-245C. cAMP-elevating agents forskolin and 8-Br-cAMP blocked EMT. However, cAMP blockers H89 and Rp-cAMP failed to block the effect of PGD2. PGD2 did not seem to act via its metabolites as 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) levels in the medium following incubation with 3 μM PGD2 were well below the values predicted from the cross activity of the assay. Exposure to TGF-β1 induced a threefold increase in reactive oxygen species production that was completely abolished by PGD2. We conclude that 1) PGD2, but not PGI2, PGF, and TXA 2 inhibit EMT, 2) PGD2 inhibits EMT independently of DP1 and DP2 receptors, and 3) PGD2 exhibits antioxidant property which may, in part, account for the antifibrotic action of this PG.

Original languageEnglish (US)
Pages (from-to)F1332-F1342
JournalAmerican Journal of Physiology - Renal Physiology
Volume291
Issue number6
DOIs
StatePublished - Dec 14 2006

Keywords

  • Madin-Darby canine kidney cells
  • Reactive oxygen species
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Urology

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