Oxytocin induced epithelium-mesenchimal transition through Rho-ROCK pathway in ARPE-19 cells, a human retinal pigmental cell line

Abstract

Previous reports suggest that oxytocin receptors (OXTRs) are expressed in the retinal pigment epithelium in primates. Oxytocinergic signaling activates the Rho-ROCK pathway, which reorganizes the actin cytoskeleton and alters other cellular biophysical characteristics. Such changes could be involved in the epithelial–mesenchymal transition and development of proliferative vitreous retinopathy. Here, we investigated whether oxytocin (OXT) binding to OXTRs in the retinal pigment epithelium can induce Rho-ROCK-mediated cellular activity. We performed four different assays of Rho-ROCK signaling in a human retinal pigment epithelium cell line (ARPE-19) such as induction of actin fibers, wound healing, cell growth, and collagen gel contraction. The assays were performed with or without OXT (100 nM) exposure, as well as with exposure to ripasudil, a specific ROCK inhibitor. The actin stress fiber formation, a phenotype mediated by activated Rho GTPase, was induced by OXT. OXT also accelerated wound closure 19 h after administration, increased cell growth 24 h afterwards, and induced stronger collagen gel contractions. All four cellular responses were inhibited with the addition of 50 μM ripasudil. Taken together, OXT-mediated activation of Rho-ROCK signal transduction could play a role in regulating epithelial–mesenchymal transition in the retinal pigment epithelium, and increase the possibility of subsequent proliferative vitreous retinopathy after vitrectomy.