EGFR-MEDIATED CORNEAL EPITHELIAL WOUND HEALING

EGFR 介导的角膜上皮伤口愈合

• 批准号: 7959981
• 负责人: BRIAN P. CERESA
• 金额: $ 10.6万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959981
• 关键词: Area; Blocking Antibodies; Cell physiology; Computer Retrieval of Information on Scientific Projects Database; Cornea; Corneal Injury; EGF gene; Epidermal Growth Factor Receptor; Epithelial Cells; Event; Funding; Grant; Homeostasis; Impaired wound healing; Institution; Ligands; Location; Mediating; Mentors; Molecular; Oklahoma; Pathway interactions; Phosphorylation; Process; Recycling; Reporting; Research; Research Personnel; Resources; Signal Transduction; Source; Staging; Stratification; Testing; United States National Institutes of Health; Vision research; Work; Wound Healing; base; cell motility; corneal epithelium; inhibitor/antagonist; receptor; small molecule; trafficking

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. Based on our own findings and the work of others, 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. In the first aim of this proposal, we will study other endogenous EGFR ligands that have been reported to be more potent activators of corneal wound healing. We hypothesize that these ligands promote different endocytic trafficking itineraries of the EGFR than EGF (i.e. recycling rather than degradation) and this is the basis of their enhance wound healing. In the second aim, we will disrupt EGFR endocytic trafficking at discrete stages along the endocytic pathway and assess the magnitude and duration of the EGFR phosphorylation, effector signaling, and cell physiology. These findings will indicate whether enrichment of the activated receptor at discrete endocytic location will specifically promote the molecular and cellular events associated with corneal wound healing.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 角膜上皮伤口愈合和体内平衡受 EGFR 活性调节。 该过程由三种细胞变化介导：细胞迁移、增殖和分层。通过小分子抑制剂或阻断抗体抑制配体刺激的 EGFR 激活，会导致所有三种细胞变化减少以及伤口愈合受损。 根据我们自己的发现和其他人的工作，我们假设可以通过促进 EGFR 介导的信号增强细胞迁移来增强角膜伤口愈合。为了检验这一假设，我们必须在分子和细胞水平上了解 EGFR 介导的信号传导。这些信息将用于靶向促进上皮细胞迁移的分子和机制，最终可以加速受损区域的覆盖和受伤角膜的愈合。 在本提案的第一个目标中，我们将研究其他内源性 EGFR 配体，据报道这些配体是角膜伤口愈合更有效的激活剂。我们假设这些配体促进 EGFR 与 EGF 不同的内吞运输行程（即回收而不是降解），这是它们增强伤口愈合的基础。 在第二个目标中，我们将在内吞途径的不同阶段破坏 EGFR 内吞运输，并评估 EGFR 磷酸化、效应信号传导和细胞生理学的程度和持续时间。 这些发现将表明活化受体在离散内吞位置的富集是否会特异性促进与角膜伤口愈合相关的分子和细胞事件。