角膜损伤修复与Notch信号通路

Corneal wound healing and the Notch signaling pathway

Notch信号通路在胚胎期细胞命运转归和成体组织稳态的维持中起重要作用。各种研究已经证明Notch信号通路在角膜损伤后修复及角膜生理性稳态的维持中有重大意义,角膜缘干细胞主要通过抑制Notch信号通路来抑制细胞的分化和增生;在角膜上皮早期修复阶段生理性下调促进细胞迁移和伤口覆盖,后期修复阶段生理性上调与防止角膜上皮细胞过度分层和维持细胞分化相关;角膜基质损伤后纤维化与Notch信号通路相关;角膜内皮损伤后转化生长因子-β(TGF-β)诱导的内皮-间质转化(EnMT)过程有Notch信号通路的直接参与;此外,Notch信号通路与14-3-3σ、表皮生长因子受体(EGFR)、Sirt6、微小RNA(miRNA)、基质金属蛋白酶(MMPs)在角膜上皮稳态维持、角膜上皮分化、角膜基质过度炎症反应、角膜新生血管生成等存在相互作用。本文就Notch信号通路在角膜各层损伤修复中的功能进行综述。

The Notch signaling pathway plays an important role in cell fate and homeostasis.Various studies have proved that the Notch signaling pathway has strong effects on corneal wound healing and the maintenance of corneal homeostasis.Limbal stem cells inhibit differentiation and proliferation by inhibiting the Notch signaling pathway.Physiologic downregulation promotes cell migration and wound coverage in the early stage of corneal epithelial repair,and physiologic upregulation in the late stage of corneal epithelial repair is related to preventing excessive stratification of corneal epithelial cells and maintaining cell differentiation.Fibrosis is correlated with Notch after corneal stromal injury.The Notch signaling pathway is directly involved in the endothelial-to-mesenchymal transition induced by transforming growth factor-βafter corneal endothelial injury.In addition,there are interactions between the Notch signaling pathway and 14-3-3 sigma,epidermal growth factor receptor,Sirt6,microRNA,and matrix metalloproteinases in maintaining corneal epithelial homeostasis,corneal epithelial differentiation,corneal stromal excessive inflammatory response,corneal neovascularization,etc.This review summarizes the function of the Notch signaling pathway in corneal wound healing.