JUNCTIONS CYTOSKELETON AND MATRIX OF THE ORAL EPITHELIUM

细胞骨架和口腔上皮基质的连接

• 批准号: 6176139
• 负责人: JONATHAN C. JONES
• 金额: $ 75.88万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176139
• 关键词: cell adhesion; cell migration; epithelium; extracellular matrix; intercellular connection; oral mucosa

During the development of periodontal disease, the junctional epithelium undergoes an aberrant migration over the tooth surface. In addition, a pocket is formed between the tooth and epithelium which can harbor bacteria. A combination of bacterial infection and inflammation results in epithelial and connective tissue destruction, leading to loosening of a tooth and eventual tooth loss. We propose that the migration of epithelial cells which is part of the pathology of periodontal disease involves modulation in those elements of the cytoskeleton, cell-cell and cell-matrix adhesive machinery which contribute to epithelial tissue homeostasis. To this end, in this application, we intend to study the dynamics and functions of the keratin elements of the cytoskeleton, desmosomal and hemidesmosomal cell junctions and a laminin component of the extracellular matrix. The proposal details a multidisciplinary, interdependent series of studies from four investigators at Northwestern University Medical School. Project 1, "Laminin-5 and hemidesmosomes in oral epithelial cells" will involve identification of the functional domains of laminin-5 and its role in nucleation of assembly of hemidesmosomes which tether oral epithelial cells to the tooth surface and to the gingival connective tissue. In addition, the nature of laminin-5-cell surface interactions will be evaluated. In Project 2, "Effect of laminin-5 processing on oral epithelial cells", normal processing of laminin-5 as well as its degradation via proteinases present in the oral cavity will be studied. Analyses of the function of laminin-5 fragments that result from matrix degradation will be evaluated at the cell biological level. Project 3, "Cytoskeletal-cell surface interactions in oral epithelia cells" will investigate the dynamic aspects of keratin networks in oral epithelial cells and the molecular mechanisms underlying keratin- cell surface associations. In Project 4, "Cell-cell junction structure and dynamics in oral epithelia", molecular genetic approaches will be used to investigate protein-protein interactions in desmosomes which link oral epithelial cells together into sheets. In addition, growth factor and proteinase regulation of junction structure will be studies. These studies are expected to provide new insights into the role of cytoskeletal, junctional and matrix proteins in the maintenance of oral epithelial tissue integrity and their potential contribution to the development of periodontal disease.

在牙周病的发展过程中，交界处 上皮细胞在牙齿表面发生异常迁移。 此外，牙齿和上皮之间还形成了一个口袋。 其中可能藏有细菌。细菌感染的组合 炎症导致上皮和结缔组织 破坏，导致牙齿松动并最终导致牙齿松动 损失。我们认为，上皮细胞的迁移是 牙周病的部分病理机制涉及调节 细胞骨架、细胞-细胞和细胞-基质的那些元素 有助于形成上皮组织的粘合机械 动态平衡。为此，在本申请中，我们打算研究 角蛋白成分的动态和功能 细胞骨架、桥粒和半桥粒细胞连接和 细胞外基质中的层粘连蛋白成分。这项建议 详细介绍了一系列相互依赖的多学科研究 西北大学医学院的四名调查人员。 项目1，“口腔上皮中的层粘连蛋白-5和半桥粒 细胞“将涉及识别的功能域 层粘连蛋白-5及其在组装成核中的作用 将口腔上皮细胞系在牙齿上的半桥粒 表面和牙龈结缔组织。此外， 将评估层粘连蛋白-5-细胞表面相互作用的性质。在……里面 项目2，“层粘连蛋白-5处理对口腔上皮细胞的影响”， 层粘连蛋白-5的正常加工及其降解 将研究口腔中存在的蛋白水解酶。分析了 基质产生的层粘连蛋白-5片段的功能 降解将在细胞生物学水平上进行评估。项目 3、《口腔上皮细胞中细胞骨架-细胞表面的相互作用》 我将研究口腔角蛋白网络的动态方面 上皮细胞和角蛋白的分子机制- 细胞表面联结。项目4，“细胞-细胞连接” 口腔上皮细胞的结构和动力学“，分子遗传学 这些方法将被用来研究蛋白质之间的相互作用。 在桥粒中，它将口腔上皮细胞连接成片状。 此外，生长因子和蛋白水解酶对连接的调节 将对结构进行研究。这些研究有望提供 对细胞骨架、连接和基质作用的新见解 蛋白质在维持口腔上皮组织完整性和 它们对牙周发育的潜在贡献 疾病。