As shown hesperidin suppresses TGF-β2-induced proliferation and epithelial-mesenchymal transition of retinal pigment epithelial cells

This study investigates the potential therapeutic effects and molecular mechanisms of hesperidin treatment on cell migration and epithelial-mesenchymal transition, key stages of proliferative vitreoretinopathy (PVR). Human retinal pigment epithelial cells (ARPE-19) were treated with 10 ng/ml transforming growth factor-beta 2 (TGF-beta 2) alone or in combination with 1.56 mu M hesperidin for 48 h. The impact of treatment on cell migration was evaluated using a wound healing assay. Apoptosis was assessed using DNA staining. mRNA and protein expression were evaluated using real-time PCR and Western blot, respectively. Hesperidin inhibits the proliferation and transformation of the cells by inducing apoptosis and reverses the cell morphology modified by TGF-beta 2. Hesperidin inhibits cell migration induced by TGF-beta 2. Upon treatment with hesperidin, the levels of mesenchymal markers upregulated by TGF-beta 2, such as MMP-1, -2, -9, fibronectin, alpha-SMA and the transcription factors Snail, Slug and ZEB-1, were downregulated. Conversely, the epithelial marker E-cadherin is upregulated with hesperidin treatment. Additionally, TIMP-1 and TIMP-2 expression levels, which are downregulated, increase with the treatment. These results suggest that hesperidin may inhibit the migration and EMT processes of RPE cells involved in the development of PVR, indicating its potential as a therapeutic agent for treating PVR.