EGFR-MEDIATED CORNEAL EPITHELIAL WOUND HEALING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 角膜上皮损伤的愈合和动态平衡受EGFR活性的调节。这一过程由三种细胞变化来调节：细胞迁移、增殖和层化。通过小分子抑制剂或封闭抗体抑制配体刺激的EGFR激活，会导致所有这三种细胞变化的减少，并损害伤口愈合。尽管有证据表明，表皮生长因子受体对角膜上皮细胞动态平衡和伤口愈合是必要的和充分的，但表皮生长因子的治疗作用有限。我们假设，通过促进EGFR介导的促进细胞迁移的信号，可以促进角膜伤口的愈合。为了验证这一假说，我们必须在分子和细胞水平上理解EGFR介导的信号转导。这些信息将被用于靶向促进上皮细胞迁移的分子和机制，这最终可以加速受损区域的覆盖和受伤角膜的愈合。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Corneal epithelial wound healing and homeostasis is regulated by EGFR activity. This process is mediated by three cellular changes: cell migration, proliferation, and stratification. Inhibition of ligand-stimulated EGFR activation, either through small molecule inhibitors or blocking antibodies, results in a decrease in all three cellular changes as well as impaired wound healing. Despite evidence that the EGFR is necessary and sufficient for corneal epithelial homeostasis and wound healing, EGF has limited therapeutic utility. We hypothesize that corneal wound healing can be enhanced by promoting EGFR-mediated signals that enhance cell migration. To test this hypothesis, we must understand EGFR-mediated signaling on the molecular and cellular level. This information will be used to target molecules and mechanisms that promote epithelial cell migration, which can ultimately accelerate coverage of the damaged area and healing of the wounded cornea.