eupatilin and Vitreoretinopathy--Proliferative

The main characteristic of proliferative vitreoretinopathy (PVR) is migration, adhesion, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE). Eupatilin is a naturally occurring flavone that has the potential to inhibit cell proliferation and EMT. However, its efficacy on the PVR model induced by transforming growth factor-2 (TGF-β2) is unknown. In this study, the potential effect of eupatilin on proliferation and EMT in the treatment of RPE was investigated.. Serum starved human RPE cells (ARPE-19) were treated with 10 ng/ml TGF-β2 alone or co-treated with 25 μM eupatilin for 48 h. Quantitative real-time PCR and Western blot analysis were used to assess targets at the mRNA and protein expression level, respectively. Apoptosis and cell cycle progression was assessed by image-based cytometry. The effect of treatment on cell migration was evaluated by wound healing assay.. Eupatilin inhibited TGF-β2-induced RPE cell proliferation via regulating the cell cycle and inducing apoptosis. TGF-β2 upregulated mRNA expression of mesenchymal markers fibronectin and vimentin was significantly downregulated by the treatment, while the epithelial markers E-cadherin and occludin expression was upregulated. The therapy significantly suppressed TGF-β2 encouraged cell migration through downregulating the expression of transcription factors Twist, Snail, and ZEB1 induced by TGF-β2. Furthermore, eupatilin significantly inhibited the expression of MMP-1, -7, and -9, and suppressed NF-κB signalling.. These results suggest that eupatilin could inhibit the proliferation and transformation into fibroblast-like cells of RPE cells; thus the agent may be a potential therapeutic value in treating PVR.

Topics: Antigens, CD; Cadherins; Cell Line; Cell Physiological Phenomena; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibronectins; Flavonoids; Humans; Matrix Metalloproteinases; Nuclear Proteins; Occludin; Retinal Pigment Epithelium; Snail Family Transcription Factors; Transforming Growth Factor beta2; Twist-Related Protein 1; Vimentin; Vitreoretinopathy, Proliferative; Zinc Finger E-box-Binding Homeobox 1