Suppression of Epithelial-Mesenchymal Transition by Prostaglandin E2 in Retinal Pigment Epithelial Cells

Background/Aims: An epithelial to mesenchymal transition of retinal pigment epithelium (RPE) cells plays an important role in the formation of proliferative fibrocellular membranes in individuals with proliferative retinopathy. Prostaglandin E2 (PGE2 ) exhibits various physiological actions including both pro- and anti-inflammatory effects. We have now investigated the effect of PGE2 on the epithelial-mesenchymal transition (EMT) of mouse RPE cells and fibrotic reactions in a type I collagen gel. Methods: Mouse RPE cells were incubated in three dimentional type 1 collagen gel culture system with transforming growth factor (TGF)-β2 (1ng/ml) in the absence or presence of PGE2 at various concentration. The expression of α-smooth muscle actin as well as matrix metalloproteinase (MMP)-3, the phosphorylation of Smad2, paxillin were examined by immunoblot analysis. The release of MMP-2 and MMP-9 was examined by gelatin zymography. Results: PGE2 inhibited the TGF-β2–induced contraction of collagen gels mediated by RPE cells in concentration dependent manner. The expression of α–smooth muscle actin and fibronectin as mesenchymal markers was inhibited. The release of MMP–2 and MMP-9 as well as the phosphorylation of Smad2 and paxillin induced by TGF-β2 in RPE cells were also attenuated by PGE2 . Conclusion: PGE2 may inhibit the contraction of proliferative fibrocellular membranes that can lead to retinal detachment in individuals with progressive vitreoretinal diseases.