Suppression of Epithelial-Mesenchymal Transition by Prostaglandin E_2 in Retinal Pigment Epithelial Cells

Orita T ； Kimura K ； Kohata Y ； Sakuma A ； Fujitsu Y ； Wakuta M ； Sonoda KH

《International Journal of Ophthalmology & Eye Science (IJOES)》 4卷3期 (2016/04) Pp. 192-197

https://doi.org/10.19070/2332-290X-1600039

摘要

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 E_2 (PGE_2) exhibits various physiological actions including both pro- and anti-inflammatory effects. We have now investigated the effect of PGE_2 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 PGE_2 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: PGE_2 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 PGE_2. Conclusion: PGE_2 may inhibit the contraction of proliferative fibrocellular membranes that can lead to retinal detachment in individuals with progressive vitreoretinal diseases.

關鍵字

Retinal Pigment Epithelial Cell ； TGF-Β2 ； Epithelial-Mesenchymal Transition ； Collagen Gel Contraction ； Prostaglandin E2