Reciprocal interaction between epithelial cells and keratocytes in neurotrophic keratopathy

在临床上，角膜上皮缺损常持续存在于那些失去角膜知觉的患者中。此外，上皮缺陷的持续性导致角膜溃疡，即过度的胶原降解。我们已经报道，感觉神经递质，P物质刺激角膜上皮细胞迁移的IGF-1的存在。在这个研究项目中，我们发现了以下几点。1)P物质和IGF-1的协同作用需要蛋白激酶C、酪氨酸激酶、磷酸肌醇3-激酶和p38丝裂原活化蛋白激酶的参与。2)小GTP结合蛋白Rho参与了角膜上皮迁移的刺激。3)层粘连蛋白是一种基底膜蛋白，在创伤愈合过程中，它调节角膜上皮细胞间粘附器连接蛋白的表达。4)角膜成纤维细胞和中性粒细胞通过IL-1系统协同刺激胶原降解。5)细胞因子TNF-α和IL-13刺激角膜成纤维细胞中趋化因子eotaxin的产生。6)P物质和IGF-1对角膜上皮细胞的刺激改变了各种mRNA的表达谱。

In a clinical setting, the corneal epithelial defects often persisted in those who lost corneal sensation. Furthermore, the persistence of epithelial defects leads to the corneal ulcer, that is the excess collagen degradation. We have reported that sensory neurotransmitter, substance P stimulates corneal epithelial migration in the presence of IGF-1. In this research projects, we found the followings. 1) The synergistic effects of substance P and IGF-1 require the participation of protein kinase C, tyrosine kinase, phosphoinositol 3-kinase and p38 mitogen-activated protein kinase. 2) Small GTP-binding protein, Rho, participated in the stimulation of corneal epithelial migration. 3) Laminin, one of the basement membrane proteins, regulates the expression of junctional proteins, which locate at the adhesion apparatus between the corneal epithelial cells during wound healing. 4) Corneal fibroblasts and PMN synergistically stimulate the collagen degradation through IL-1 system. 5) Cytokines, TNF-a and IL-13 stimulates production of chemokine, eotaxin, in corneal fibroblasts. 6) The stimulation of corneal epithelial cells by substance P and IGF-1 changes the expression profiles of various mRNAs.