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A novel regulator of corneal wound healing and Pseudomonas aeruginosa keratitis

角膜伤口愈合和铜绿假单胞菌角膜炎的新型调节剂

基本信息

批准号：
10391450
负责人：
FENG C LIN
金额：
$ 39.04万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10391450
关键词：
Activated-Leukocyte Cell Adhesion Molecule Address Affinity Anoikis Anti-Bacterial Agents Antibacterial Response Antibiotics Bacteria Binding Biological Assay CD14 Antigen CD14 gene CD6 antigen Cell Proliferation Cell Survival Cell surface Cells Chemotactic Factors Clinical Clinical Trials Contact Lenses Cornea Cultured Cells Development Disease Economics Environment Epithelial Cell Proliferation Epithelial Cells Exhibits Extended-Wear Contact Lenses Eye Eyedrops Homeostasis Human Impairment Infection Inflammation Interleukin-17 Invaded Keratitis Knock-out Knockout Mice Mediating Modeling Mus Neutrophil Infiltration Non-Malignant Pain Pathologic Pathway interactions Peptide Hydrolases Phase Physiological Plasminogen Prevention strategy Production Proteins Proto-Oncogene Proteins c-akt Pseudomonas aeruginosa Pseudomonas aeruginosa infection Publishing Reagent Recombinants Reporting Research Resistance Role Serine Protease Severities Signal Transduction Solid Neoplasm Steroids T-Lymphocyte Testing Therapeutic Agents Tissues Topical application Ulcer United States Vision Visit Work antimicrobial antimicrobial peptide base biophysical techniques corneal epithelial wound healing corneal epithelium effective therapy epithelial wound immunoregulation improved interleukin-22 knock-down microbial mouse model mucosal site mutant neoplastic cell neutrophil non-oncogenic novel novel therapeutics overexpression recombinant adenovirus recruit selective expression side effect social targeted treatment treatment strategy unpublished works wound wound treatment γδ T cells

项目摘要

Project Summary In our recently published work, we discovered that CUB-Domain-Containing Protein 1 (CDCP1) is a new and important ligand of CD6, which is a marker and a critical regulator of T cells, demonstrating a surprising role of CDCP1 in immune regulation. CDCP1 was originally discovered to be overexpressed on certain solid tumor cells, regulating tumor-cell anoikis resistance. However, the distribution of CDCP1 in the eye and its potential role in tissue homeostasis was unknown. In our latest (unpublished) work, using CDCP1 knockout (KO) mice and CDCP1 knocked down human corneal epithelial cells, we discovered that CDCP1 is highly and selectively expressed on corneal epithelial cells among all ocular cells, and that CDCP1 is critical for enhancing corneal wounding healing. In this proposed project, using the unique reagents and models that we have developed, including CDCP1-KO mice, CD6-KO mice, CDCP1-KO human corneal epithelial cells and recombinant mutant CDCP1 proteins, we will elucidate both the intrinsic and extrinsic mechanisms by which CDCP1 enhances corneal wound healing. We will also test novel CDCP1-targeted approaches as new therapeutics for accelerating corneal wound healing. The proposed work would establish a previously unknown role of CDCP1 in corneal wound healing, facilitate the development of new and effective therapies for this corneal pathological condition, and open a new avenue for research on CDCP1 and corneal homeostasis.

项目概要在我们最近发表的工作中，我们发现 CUB 域包含蛋白 1 (CDCP1) 是 CD6 的一种新的重要配体，CD6 是 T 细胞的标记物和关键调节因子，证明了 CDCP1 在免疫调节中的惊人作用。 CDCP1最初被发现在某些实体瘤细胞上过度表达，调节肿瘤细胞的失巢凋亡抵抗力。然而，CDCP1 在眼中的分布及其在组织稳态中的潜在作用尚不清楚。在我们最新（未发表）的工作中，使用CDCP1敲除（KO）小鼠和CDCP1敲除人角膜上皮细胞，我们发现CDCP1在所有眼部细胞中的角膜上皮细胞上高度选择性表达，并且CDCP1对于增强角膜伤口愈合至关重要。在这个拟议的项目中，使用我们开发的独特试剂和模型，包括CDCP1-KO小鼠、CD6-KO小鼠、CDCP1-KO人角膜上皮细胞和重组突变CDCP1蛋白，我们将阐明CDCP1增强角膜伤口愈合的内在和外在机制。我们还将测试新的CDCP1靶向方法作为加速角膜伤口愈合的新疗法。拟议的工作将确定CDCP1在角膜伤口愈合中以前未知的作用，促进针对这种角膜病理状况的新的有效疗法的开发，并为CDCP1和角膜稳态的研究开辟新途径。