Differences Between Oral and Skin Keratinocytes During Wound Healing

Epithelial cells provide barrier protection throughout the body. Although oral mucosal and skin epithelium share many morphological similarities they also exhibit distinct capacities. One significant functional difference is the wound healing response, as mucosal wounds heal more rapidly than skin (Szpaderska 2005). The structure of the oral mucosa resembles the skin in many ways. It is composed of two layers, the epithelium and connective tissue. The epithelium of the oral mucosal membrane may be keratinized or nonkeratinized depending on location. In humans and mice, the dorsum of the tongue, gingiva and hard palate are keratinized tissues. Keratinized tissue in the oral mucosa is very similar to skin, making it a good model to study healing. One important aspect of wound healing is re-epithelialization, which is restoration of the epidermis by keratinocytes. Upon injury, epithelial cells from wound edges dissolve their hemidesmosomal connections, detach from the basement membrane and move quickly across the exposed connective tissue. In the normal situation, cells just behind the wound edge undergo a proliferative and migratory burst and effectively replace keratinocytes lost as a result of injury. This tremendous proliferative and migratory capacity of keratinocytes is critical for effective wound re-epithelialization. In a study where equivalent full thickness 1mm diameter wounds are created on both the dorsal skin and tongue of the mouse, oral mucosa wounds ix exhibit re-epithelialization very rapidly, with 100% completion at 24 hours post-injury. In contrast, cutaneous wounds are less than 25% re-epithelialized at the 24 hour time point (Schrementi 2008). These data strongly suggest that the proliferative capacity of oral keratinocytes is greater than that of dermal keratinocytes. As migration is another critical aspect of re-epithelialization, in this study we investigate whether the migratory capacity of oral keratinocytes is different in comparison to skin. Evidence to support the hypothesis that differences responsible for rapid repair in oral mucosa could be intrinsic keratinocyte characteristics is available. Since keratinocytes are the major source of VEGF in the wound and produce pro-angiogenic factors in response to hypoxia, investigation of the VEGF mRNA and protein levels in isolated oral and skin keratinocytes was conducted. When subjected to hypoxia, epidermal keratinocytes produced higher levels of both VEGF protein and mRNA than did oral keratinocytes (Szpaderska 2005). These findings imply that the superior repair in oral mucosa is likely to be related to intrinsic characteristics of mucosal tissue and not to environmental factors such as temperature, salivary flow or microflora. The goal of this study was to identify innate positional differences in epithelial cells that might contribute to the site-specific response to injury.