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Oxytocin induced epithelium-mesenchimal transition through Rho-ROCK pathway in ARPE-19 cells, a human retinal pigmental cell line.
Tissue & Cell ( IF 2.6 ) Pub Date : 2020-02-08 , DOI: 10.1016/j.tice.2019.101328
Takahiro Tsuji 1 , Masaru Inatani 2 , Chiharu Tsuji 3 , Stanislav M Cheranov 3 , Kazuaki Kadonosono 4
Affiliation  

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.

中文翻译:

催产素通过ARho-19细胞(人类视网膜色素细胞系)中的Rho-ROCK途径诱导上皮-间质转化。

以前的报告表明催产素受体(OXTRs)在灵长类动物的视网膜色素上皮细胞中表达。催产素能信号转导激活Rho-ROCK通路,从而重组肌动蛋白的细胞骨架并改变其他细胞的生物物理特性。这种改变可能参与了增生性玻璃体视网膜病变的上皮-间质转化和发展。在这里,我们调查了是否催产素(OXT)绑定到视网膜色素上皮中的OXTRs可以诱导Rho-ROCK介导的细胞活性。我们在人视网膜色素上皮细胞系(ARPE-19)中进行了Rho-ROCK信号传导的四种不同测定,例如肌动蛋白纤维的诱导,伤口愈合,细胞生长和胶原凝胶收缩。在有或没有OXT(100 nM)暴露的情况下,以及在ripasudil,特定的ROCK抑制剂。OXT诱导肌动蛋白应激纤维形成,一种由活化的Rho GTPase介导的表型。OXT还可以在给药后19小时加速伤口闭合,在24小时后增加细胞生长,并诱导更强的胶原蛋白凝胶收缩。加入50μMripasudil可抑制所有四种细胞反应。两者合计,OXT介导的Rho-ROCK信号转导的激活可能在调节视网膜色素上皮的上皮-间质转化中起作用,并增加玻璃体切除术后继发性玻璃体视网膜病变的可能性。并引起更强的胶原蛋白凝胶收缩。加入50μMripasudil可抑制所有四种细胞反应。两者合计,OXT介导的Rho-ROCK信号转导的激活可能在调节视网膜色素上皮的上皮-间质转化中起作用,并增加玻璃体切除术后继发性玻璃体视网膜病变的可能性。并引起更强的胶原蛋白凝胶收缩。加入50μMripasudil可抑制所有四种细胞反应。两者合计,OXT介导的Rho-ROCK信号转导的激活可能在调节视网膜色素上皮的上皮-间质转化中起作用,并增加玻璃体切除术后继发性玻璃体视网膜病变的可能性。
更新日期:2020-02-08
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