Reciprocal interaction between epithelial cells and keratocytes in neurotrophic keratopathy

在临床上，角膜上皮缺陷通常持续存在于那些失去角膜感觉的人身上。此外，上皮缺陷的持续存在导致角膜溃疡，即过多的胶原蛋白降解。我们已经报道了感觉神经递质P物质在IGF-1存在的情况下刺激角膜上皮的迁移。在这个研究项目中，我们发现了以下几点。1) P物质与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（Laminin）是一种基底膜蛋白，在创面愈合过程中调控位于角膜上皮细胞间黏附装置的连接蛋白的表达。4)角膜成纤维细胞和PMN通过IL-1系统协同刺激胶原降解。5)细胞因子、TNF-a和IL-13刺激角膜成纤维细胞趋化因子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.