Oral Mucins as a Diagnostic Indicator and Therapeutic Treatment for Xerostomia

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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.