EPITHELIAL MATRIX INTERACTIONS IN THE CORNEA

角膜上皮基质的相互作用

• 批准号: 2161745
• 负责人: STEPHEN P SUGRUE
• 金额: $ 13.95万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2161745
• 关键词: cell adhesion; cell adhesion molecules; cell migration; chick embryo; chickens; corneal epithelium; extracellular matrix; immunoprecipitation; integrins; intercellular connection; laboratory mouse; laboratory rabbit; laboratory rat; monoclonal antibody; tissue /cell culture; wound healing

The overall goal of this proposal is to determine the role and regulation of specific adhesion molecules in (1) the maintenance of corneal epithelial integrity, (2) epithelial migration following wounding, and (3) the re-establishment of the competent epithelial barrier upon healing of the wound. Our hypothesis is that the molecular components, which function in quiescent epithelia to ensure stable cell-matrix and intercellular adhesion, become dynamically involved in more supple adhesion interactions during epithelial migration subsequent to lesion of the ocular surface. Transformations of epithelial cells during the transition from sedentary to actively migrating, may involve the disassembly of dedicated adhesion structures, movements of adhesion molecules, changes in their molecular associations, and post-translational indications of adhesion related proteins. When the wound closure has been completed, the epithelium would need to reverse the above changes and again establish a stable epithelial configuration. To reach this goal, we will use a combination of morphological, immunological, biochemical and molecular biological methods to investigate various aspects of the molecules mediating epithelial cell adhesion. We will identify and characterize some family of cell surface adhesion proteins referred to as integrins. Members of the integrin family will be studied for potential roles in cell-cell as well as cell-matrix adhesion. We will examine the means by which the epithelial cell may discriminate between adhesive interactions with other cells vs. with the extracellular matrix. A new protein has been discovered in our laboratory that may play a crucial role in the establishment of stable corneal epithelial adhesion. We present plans to further characterize this protein and to determine its relationship to the mechanism of stable epithelial cell adhesion. Finally, we will examine the role and regulation of epithelial intercellular junctional components in epithelial cell migration and the re-establishing of a competent epithelial barrier following wound closure. Study of the specific molecules involved in epithelial adhesion and their regulation under varying physiological conditions, quiescent, migrating and recently healed, will provide valuable new information which is essential to the understanding of clinical conditions characterized by the loss of epithelial adhesion.

该提案的总体目标是确定角色和监管 (1) 角膜的维护中的特异性粘附分子 上皮完整性，(2) 受伤后上皮迁移，以及 (3) 愈合后上皮屏障的重建 伤口。我们的假设是，发挥作用的分子成分 在静止的上皮细胞中，以确保稳定的细胞基质和细胞间质 粘附，动态地参与更柔软的粘附相互作用 在眼表损伤后的上皮迁移过程中。 从久坐转变过程中上皮细胞的转变 主动迁移，可能涉及专用粘附的拆卸 粘附分子的结构、运动、其分子的变化 关联和粘附相关的翻译后适应症 蛋白质。当伤口闭合完成后，上皮细胞会 需要扭转上述变化，重新建立稳定的上皮细胞 配置。 为了实现这一目标，我们将结合使用形态学、 免疫学、生化和分子生物学方法进行研究 介导上皮细胞粘附的分子的各个方面。我们 将识别和表征某些细胞表面粘附家族 蛋白质称为整合素。整合素家族的成员将是 研究了细胞与细胞以及细胞与基质粘附中的潜在作用。 我们将研究上皮细胞区分的方式 与其他细胞的粘附相互作用与与细胞外的粘附相互作用之间的关系 矩阵。我们的实验室发现了一种新的蛋白质，可能会发挥作用 在建立稳定的角膜上皮粘附方面发挥着至关重要的作用。 我们提出了进一步表征该蛋白质并确定其 与上皮细胞稳定粘附机制的关系。最后， 我们将研究上皮细胞间质的作用和调节 上皮细胞迁移和重建中的连接成分 伤口闭合后形成有效的上皮屏障。研究的 参与上皮粘附的特定分子及其调节 在不同的生理条件下，静止的、迁移的和最近的 治愈后，将提供宝贵的新信息，这对于 了解以丧失能力为特征的临床状况 上皮粘连。