IN VITRO MODEL OF CORNEAL WOUND HEALING: ROLE OF MATRIX

角膜伤口愈合的体外模型：基质的作用

• 批准号: 3266469
• 负责人: DIANE A BLAKE
• 金额: $ 10.05万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3266469
• 关键词: SDS polyacrylamide gel electrophoresis; affinity chromatography; antiserum; autoradiography; bioassay; biological models; cell adhesion molecules; cell cell interaction; cell cycle; cell migration; chemotaxis; corneal endothelium; enzyme linked immunosorbent assay; extracellular matrix; fibronectins; fluorouracil; heparin; high performance liquid chromatography; human tissue; immunofluorescence technique; inhibitor /antagonist; laboratory rabbit; model design /development; monoclonal antibody; peptides; platelets; protein biosynthesis; protein purification; protein structure function; proteoglycan; radiotracer; temperature; thrombospondins; thymidine; tissue /cell culture; wound healing

Cellular movement is required during normal embryonic growth, tissue remodeling, and wound repair. Several different classes of molecules, including growth factors, cell surface receptors, metalloproteinases, cytoskeletal elements, tumor cell-derived migration factors, and extracellular matrix molecules are involved in this process. The relationships among these factors are not well understood, but they most likely involve complex interactions between many of the molecules listed above. In the study proposed here, we wish to characterize the interactions between cells and extracellular matrix in an in vitro model system (bovine corneal endothelial cells) where the cells have been induced to migrate in response to an injury. A unique aspect of this model system is that the corneal endothelial cells migrate over a complex substratum that they have elaborated, rather than in response to a single purified matrix component. Therefore, migration in this model system is much more likely to resemble the in vivo response of the cells. Work from our own laboratory and several others has implicated a specific extracellular matrix molecule, thrombospondin, as important in the migratory response. The work from our laboratory was the first to implicate thrombospondin in corneal wound healing. In the proposed research, we will determine the ability of antibodies to thrombospondin, exogenously added thrombospondin and peptides derived from thrombospondin, and proteoglycans derived from the surface of bovine corneal endothelial cells, to modulate the migratory response in our in vitro model system. It is anticipated that these studies will provide information about how cells decipher the complex information present in the extracellular matrix. These studies will also provide information that may be useful in designing therapy to stimulate healing in the corneal endothelium.

正常胚胎生长、组织发育过程中需要细胞运动 重塑和伤口修复。 几种不同类别的分子， 包括生长因子、细胞表面受体、金属蛋白酶、 细胞骨架元件、肿瘤细胞衍生的迁移因子，以及 细胞外基质分子参与该过程。 这 这些因素之间的关系尚不清楚，但它们最 可能涉及列出的许多分子之间复杂的相互作用 多于。 在这里提出的研究中，我们希望描述 体外模型中细胞与细胞外基质之间的相互作用 系统（牛角膜内皮细胞），其中细胞已 因损伤而诱导迁移。 这其中一个独特的方面 模型系统是角膜内皮细胞在复杂的 他们详细阐述的基础，而不是针对单一的 纯化的基质成分。 因此，该模型系统中的迁移是 更有可能类似于细胞的体内反应。 工作 来自我们自己的实验室和其他几个实验室的研究表明了一个特定的 细胞外基质分子，血小板反应蛋白，在 迁移反应。 我们实验室的工作是第一个 表明血小板反应蛋白与角膜伤口愈合有关。 在提议的 研究，我们将确定抗体对血小板反应蛋白的能力， 外源添加的血小板反应蛋白和肽 血小板反应蛋白和来自牛表面的蛋白聚糖 角膜内皮细胞，调节我们体内的迁移反应 体外模型系统。 预计这些研究将提供 有关细胞如何破译存在于细胞中的复杂信息的信息 细胞外基质。 这些研究还将提供信息 这可能有助于设计刺激愈合的疗法 角膜内皮。