Oral Mucins as a Diagnostic Indicator and Therapeutic Treatment for Xerostomia

口腔粘蛋白作为口干症的诊断指标和治疗方法

• 批准号: 7772225
• 负责人: DAVID JOHN CULP
• 金额: $ 12.82万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-13 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7772225
• 关键词: Antibodies; Biochemical; Biological; Biological Assay; Body part; Burning Mouth Syndrome; Cell Line; Cheek structure; Complex; Control Groups; Core Protein; Data; Diagnostic; Disease; Disease Progression; Dryness; Environment; Epithelial Cells; Esthesia; Funding; Gastrointestinal tract structure; Gene Expression; Genes; Genitourinary system; Glycoproteins; Human; Hydration status; Lead; Link; Liquid substance; Lubrication; Mouth Diseases; Mucins; Mucous body substance; Normal Range; Oligosaccharides; Oral; Oral cavity; Palate; Patients; Perception; Pharmacologic Substance; Pilot Projects; Production; Proteins; Quality of life; RNA; Role; Saliva; Salivary; Salivary Glands; Sampling; Sjogren' s Syndrome; Staging; Surface; Syndrome; Techniques; Testing; Therapeutic; Tissues; Transcript; Xerostomia; base; fluid flow; gene therapy; improved; insight; keratinocyte; oral cavity epithelium; oral tissue; pathogen; public health relevance; research study; saliva secretion; trend

DESCRIPTION (provided by applicant): Mucins are a primary component of mucus covering those parts of the body exposed to the environment, including the airways, digestive tract, urogenital system, and the oral cavity. Mucins are generally large molecules composed of a protein core linked to multiple complex oligosaccharide chains. Mucins perform many protective functions, including hydration and lubrication of tissue surfaces as well as interaction with pathogens, either alone or as part of large complexes with other constituent proteins of saliva or mucus. In saliva, secretions from salivary glands contribute at least two mucins. Two other mucins have been localized to epithelial cells lining oral tissues such as the cheeks and palate. In preliminary experiments with human salivary gland RNA, we discovered multiple additional mucin transcripts in oral tissues. Given the expression of multiple mucins in the oral cavity and their role in hydration and lubrication, we hypothesize that the subjective complaint of oral dryness (xerostomia) by patients suffering from oral diseases, such as Sjvgren's syndrome and Burning Mouth Syndrome, is associated with an alteration in expression of one or more mucins by the oral epithelium and/or salivary glands. A change in mucin expression may explain why many patients complain of a dry mouth (xerostomia), yet they produce a normal flow of saliva fluid. To initially test our hypothesis and provide preliminary data for a subsequent RO1 application, we will compare mucin gene expression in samples of saliva and oral epithelial cells between healthy human controls and three separate patient groups that present with xerostomia (10 subjects per group). These patient groups include those with Burning Mouth Syndrome and two groups of patients with Sjvgren's syndrome; those that are hyposalivary and those with flow in the normal range. Our pilot study has two specific aims. Aim one is to develop antibody-based assays of mucin expression as well as techniques to collect oral epithelial cells. Aim two is to determine differences between the control group and each patient group in the expression of mucins within whole saliva and/or of mucins associated with oral epithelial cells derived from two different regions of the oral cavity. Results from this pilot study are necessary to justify funding for a subsequent larger study focused on those mucins that display either a statistical difference or a trend for altered expression between the control and one or more patient group(s). Identification of the altered expression of one or more mucins in association with subjective oral dryness may ultimately lead to: 1) Improved diagnostics of patients in the early stages of oral disease as well as during subsequent disease progression, when salivary flow becomes compromised; 2) Biochemical therapies to relieve oral dryness, either through addition of appropriate mucin(s) or mucin surrogates to oral rinses; 3) Gene therapies to appropriate oral targets to counteract changes in mucin expression; or 4) Further insights into biological mechanisms that lead to disease initiation or progression by delineation of factors that control mucin gene expression. PUBLIC HEALTH RELEVANCE: Diseases of the oral cavity in many instances are associated with the perception of a dry mouth (either with or without a marked decrease in saliva production) and a concomitant decrease in the quality of life. Identification of the altered expression of one or more mucins in association with the subjective complaint of oral dryness may ultimately lead to: 1) Improved diagnostics of patients during the early stages of oral disease, as well as during subsequent disease progression when salivary flow becomes compromised; 2) Therapies to relieve oral dryness, either through addition of appropriate mucin(s), mucin components, or mucin surrogates to oral rinses; or 3) Gene therapies or pharmaceuticals to counteract changes in the expression of mucins.

描述（由申请人提供）：粘蛋白是覆盖暴露于环境的身体部位的粘液的主要成分，包括气道、消化道、泌尿生殖系统和口腔。粘蛋白通常是由连接多个复杂寡糖链的蛋白质核心组成的大分子。粘蛋白具有许多保护功能，包括组织表面的水合和润滑以及与病原体的相互作用，无论是单独的还是作为与唾液或粘液的其他组成蛋白的大复合物的一部分。在唾液中，唾液腺的分泌物提供至少两种粘蛋白。另外两种粘蛋白定位于口腔组织内壁的上皮细胞，例如脸颊和上颚。在人类唾液腺 RNA 的初步实验中，我们在口腔组织中发现了多个额外的粘蛋白转录物。鉴于口腔中多种粘蛋白的表达及其在水合和润滑中的作用，我们假设患有干燥综合征和灼口综合征等口腔疾病的患者对口腔干燥（口干症）的主观主诉与口腔上皮和/或唾液腺的一种或多种粘蛋白表达的改变。粘蛋白表达的变化可以解释为什么许多患者抱怨口干（口干症），但他们却能产生正常的唾液流动。为了初步检验我们的假设并为后续 RO1 应用提供初步数据，我们将比较健康人类对照和三个患有口干症的独立患者组（每组 10 名受试者）之间唾液和口腔上皮细胞样本中的粘蛋白基因表达。这些患者组包括患有灼口综合症的患者和两组患有干燥综合征的患者；那些唾液腺功能低下的人和那些流量在正常范围内的人。我们的试点研究有两个具体目标。目标一是开发基于抗体的粘蛋白表达测定以及收集口腔上皮细胞的技术。目标二是确定对照组和每个患者组之间在整个唾液中的粘蛋白和/或与源自口腔两个不同区域的口腔上皮细胞相关的粘蛋白的表达方面的差异。这项试点研究的结果对于证明为后续更大规模的研究提供资金是必要的，该研究的重点是那些在对照组和一个或多个患者组之间表现出统计差异或表达改变趋势的粘蛋白。识别与主观口腔干燥相关的一种或多种粘蛋白的表达改变可能最终导致：1）改进对口腔疾病早期阶段以及随后的疾病进展期间唾液流量受损的患者的诊断； 2) 通过在口腔冲洗液中添加适当的粘蛋白或粘蛋白替代物来缓解口腔干燥的生化疗法； 3) 针对适当口腔靶标的基因疗法，以抵消粘蛋白表达的变化； 4) 通过描述控制粘蛋白基因表达的因素，进一步深入了解导致疾病发生或进展的生物学机制。 公共卫生相关性：在许多情况下，口腔疾病与口干的感觉（无论是否伴有唾液分泌明显减少）以及随之而来的生活质量下降有关。识别一种或多种粘蛋白表达的改变与口腔干燥的主观主诉相关，最终可能会导致：1）在口腔疾病的早期阶段以及唾液流受损时的后续疾病进展期间改进对患者的诊断; 2) 通过在口腔冲洗液中添加适当的粘蛋白、粘蛋白成分或粘蛋白替代物来缓解口腔干燥； 3) 基因疗法或药物来抵消粘蛋白表达的变化。