Membrane Bound Mucins in Salivary Glands and Saliva

唾液腺和唾液中的膜结合粘蛋白

• 批准号: 6766944
• 负责人: GWYNNETH D OFFNER
• 金额: $ 20.13万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2006-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6766944
• 关键词: bacteria infection mechanism; cell line; clinical research; enzyme linked immunosorbent assay; epithelium; gene expression; host organism interaction; human tissue; immunocytochemistry; membrane proteins; mucins; oral bacteria; oral mucosa; protein localization; protein protein interaction; saliva; salivary glands; western blottings; yeast two hybrid system

DESCRIPTION (provided by applicant): Mucins are heavily glycosylated proteins, which are synthesized and secreted by epithelial cells lining the gastrointestinal, respiratory and genitourinary tracts. To date, thirteen distinct mucin genes have been identified and these can be divided into two distinct classes, gel-forming mucins and membrane-bound mucins. In salivary secretions, mucins facilitate speech and swallowing, protect oral surfaces against microbial, chemical and mechanical injury and contribute to a selectively permeable diffusion barrier between underlying surfaces and the external environment. These functions have largely been attributed to the major gel-forming mucin in saliva, MG1. Nevertheless, we have recently shown that two membrane-bound mucins, MUC1 and MUC4, are expressed in all major salivary glands, including the parotid glands. While virtually nothing is known about the expression and functional properties of membrane-bound mucins in salivary glands and saliva, our hypothesis is that these molecules form an integral part of the oral host-defense system in the protection of oral epithelial surfaces. The overall goal of this project is to understand the mechanisms by which this occurs. The Specific Aims of this project are to: 1) determine the expression pattern of the membrane-bound mucins MUC1 and MUC4 in major and minor salivary glands and in different glandular secretions. 2) characterize the nature of the interactions between membrane-bound and gel-forming mucins and 3) investigate the role of MUC I and MUC4 in protection of oral epithelial surfaces from microbial attack.

描述(申请人提供)：粘蛋白是高度糖基化的蛋白质，由胃肠道、呼吸道和泌尿生殖道内的上皮细胞合成和分泌。到目前为止，已经鉴定了13个不同的粘蛋白基因，这些基因可以分为两个不同的类别，即凝胶形成的粘蛋白和膜结合的粘蛋白。在唾液分泌物中，粘蛋白促进说话和吞咽，保护口腔表面免受微生物、化学和机械损伤，并在底层表面和外部环境之间形成选择性可渗透的扩散屏障。这些功能在很大程度上归因于唾液中主要的凝胶形成粘蛋白MG1。然而，我们最近发现，两种膜结合粘蛋白MUC1和MUC4在所有主要唾液腺中都有表达，包括腮腺。虽然对唾液腺和唾液中膜结合粘蛋白的表达和功能特性几乎一无所知，但我们的假设是，这些分子构成了口腔上皮表面保护的口腔宿主防御系统的组成部分。这个项目的总体目标是了解这种情况发生的机制。 本项目的具体目的是：1)确定膜结合粘蛋白MUC1和MUC4在大小涎腺和不同腺体分泌物中的表达模式。2)表征膜结合粘蛋白和凝胶形成粘蛋白之间相互作用的性质；3)研究MUC I和MUC4在保护口腔上皮细胞表面免受微生物攻击中的作用。