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Gene expression profiles during scarless healing of human palatal mucosa Habijanac, Tara Marie

Abstract

Scarless healing of adult wounds is not well understood. Unlike human skin, oral masticatory mucosa heals largely by regeneration rather than scar formation. For a better understanding of healing by regeneration, we compared gene expression profiles of human mucosal wounds 1-, 3-, and 7-day-postwounding to that of normal non-wounded mucosa in three healthy volunteers. Clinical and histological healing was followed in additional volunteers for up to 60 days. The majority of the mucosal wounds healed with regeneration as the wounds at 60 days or later were no longer clinically or histologically detectable. At day one, a large number of genes showed a change in expression (988 genes). Expression levels of extracellular matrix proteins were down-regulated while genes in several categories including cytokines, cell motility and immune response were up-regulated. Gene ontology analysis of 3-day-old wounds revealed up-regulation of many categories including proteinase inhibitors, calcium binding categories. In 7-day-old wounds, genes for the extracellular matrix proteins and cytoskeletal structural proteins were highly expressed. Interestingly, some genes with the largest increase in expression showed no major decline from day one to seven. These included matrix metalloproteinase-1, serine proteinase inhibitor B l and a novel gene in the context of wound healing, carcinoembryonic antigen-related cell adhesion molecule-6 (Ceacam-6). In early wounds, Ceacam-6 protein was expressed by basal and suprabasal keratinocytes at the wound margin. After 7 days post-wounding, expression of Ceacam-6 in keratinocytes declined but was induced in granulation tissue fibroblasts that continued to express Ceacam-6 until day 28. The function of Ceacam-6 in oral cells during wounding remains unravelled but could involve regulation of self-defence against bacteria and inhibition of anoikis. To conclude, the present study represents one of the first large-scale gene expression studies comparing different phases of regenerating human mucosal wounds. Future studies are needed to directly compare gene expression profiles of healing scar-forming skin wounds to regenerating oral wounds.

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