Queensland Eye Institute, 140 Melbourne Street, South Brisbane, Queensland, 4101, Australia.
Queensland Eye Institute, 140 Melbourne Street, South Brisbane, Queensland, 4101, Australia; School of Biomedical Science, Queensland University of Technology, 2 George Street, Brisbane, Queensland, 4001, Australia; Institute of Health and Biomedical Innovation, 60 Musk Avenue, Kelvin Grove, Queensland, 4059, Australia.
Exp Eye Res. 2018 May;170:92-100. doi: 10.1016/j.exer.2018.02.017. Epub 2018 Feb 21.
The corneal endothelium is a monolayer of epithelial cells that lines the posterior surface of the cornea and is essential for maintenance of corneal transparency. Wound healing within the corneal endothelium typically occurs through cell spreading and migration rather than through proliferation. The mechanisms that control corneal endothelial cell migration are unclear. In this study we demonstrate that cultures of corneal endothelial cells display reduced migration in scratch wound assays, and reduced levels of E-cadherin mRNA, following suppression of ligand-activated Eph receptor signalling by treatment with lithocholic acid. Two Eph receptors, EphA1 and EphA2, were subsequently detected in corneal endothelial cells, and their potential involvement during migration was explored through gene silencing using siRNAs. EphA2 siRNA reduced levels of mRNA for both EphA2 and N-cadherin, but increased levels of mRNA for both EphA1 and E-cadherin. No effect, however, was observed for EphA2 siRNA on migration. Our results indicate a potential role for Eph receptor signalling during corneal endothelial cell migration via changes in cadherin expression. Nevertheless, defining a precise role for select Eph receptors is likely to be complicated by crosstalk between Eph-mediated signalling pathways.
角膜内皮是一层上皮细胞,排列在角膜的后表面,对于维持角膜透明度至关重要。角膜内皮中的伤口愈合通常通过细胞展开和迁移而不是通过增殖来发生。控制角膜内皮细胞迁移的机制尚不清楚。在这项研究中,我们证明在用石胆酸处理以抑制配体激活的 Eph 受体信号后,角膜内皮细胞在划痕伤口测定中显示出迁移减少,并且 E-钙粘蛋白 mRNA 水平降低。随后在角膜内皮细胞中检测到两种 Eph 受体 EphA1 和 EphA2,并且通过使用 siRNA 进行基因沉默来探索它们在迁移过程中的潜在作用。 EphA2 siRNA 降低了 EphA2 和 N-钙粘蛋白的 mRNA 水平,但增加了 EphA1 和 E-钙粘蛋白的 mRNA 水平。然而,EphA2 siRNA 对迁移没有影响。我们的结果表明,Eph 受体信号在角膜内皮细胞迁移中可能通过改变钙粘蛋白表达起作用。然而,通过 Eph 介导的信号通路之间的串扰来定义特定 Eph 受体的确切作用可能很复杂。