TREFOIL FACTORS AND ORAL MUCOSAL WOUND HEALING

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Trefoil factors are a family of three small peptides secreted into the gut lumen with mucins that play a critical role in restoration of epithelial integrity following injury to gut epithelium. We propose to test the hypothesis that one or more of the trefoil factors also contribute to maintenance of epithelial integrity in the oral cavity. The specific aims of this project are: 1. To determine whether epithelial cells lining the oral cavity make any of the 3 defined human trefoil factors (pS2/TFF1, SP/TFF2, and ITF/TFF3) using a combination of RT-PCR and in situ hybridization. 2. To determine whether oral cavity epithelial cell lines can respond to recombinant intestinal trefoil factor (ITF/TFF3) with changes in their motogenic properties in a well-standardized in vitro assay for cell migration and epithelial wound healing. 3. To analyze oral cavity epithelial cell lines for the presence of, surface receptors capable of binding to ITF/TFF3 using a fusion protein that includes a consensus sequence for site-specific enzymatic biotinylation. Identification of additional natural polypeptides that favor healing of ulcerative lesions on oral mucosa is a first step towards development of new therapeutic approaches to the important clinical problems of recurrent severe apthous ulcers and chemotherapy-induced mucositis.