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The protocols for the use of human tissues were approved by the local ethical committee

The protocols for the use of human tissues were approved by the local ethical committee. in benign keratoses of lingual mucosa induction of K2e along LXR-623 with K1 and K10 was observed. In mild-to-moderate oral dysplasia with orthokeratinization, K2e was highly expressed compared with parakeratinized areas but in severe dysplasia as well as in oral squamous cell carcinoma, K2e expression was undetectable. Taken together, the data suggest that K2e expression in skin is usually sensitive to keratinocyte activation but its up-regulation in oral lesions is usually a reflection of the degree of orthokeratinization. The normal adult epidermis is usually a self-renewing tissue consisting of 10 to 20 layers in which cell proliferation is usually primarily restricted to the basal layer. When keratinocytes commit to differentiate, they LXR-623 down-regulate cell surface integrins to lose adhesiveness, leave the basal layer, exit the cell cycle, 1,2 and undergo a program of terminal differentiation as they move through the suprabasal layers to the tissue surface. 3 During this journey the keratinocytes undergo a series of physiological and morphological changes that culminate in the production of dead, flattened enucleated squames that are shed and replenished by differentiating keratinocytes. 4,5 In the oral cavity, however, huge regional variations are found in the LXR-623 degree and type of keratinization. Orthokeratinized epithelium comparable to that in skin is seen in the hard palate, whereas other regions are either parakeratinized (gingiva) or nonkeratinized (buccal mucosa). 6 Injury to the epidermis activates a homeostatic response resulting in inflammation, re-epithelialization, followed by tissue remodeling. 7,8 Several studies have suggested release of interleukin-1 from keratinocytes at the wound site as the initial trigger for the inflammatory reaction. This serves as an autocrine signal to surrounding keratinocytes and paracrine signal to other cells, such as fibroblasts, endothelial cells, and lymphocytes resulting in a pleiotropic effect on them. 9,10 The changes in gene expression that accompany re-epithelialization are similar to those seen in other disorders associated with hyperproliferation such as psoriasis, contact dermatitis, and squamous cell carcinoma (SCC) suggesting considerable overlap in the signaling cascades. The development of a normal scar is dependent around the reversal of expression of these genes at the wound site. However, in some cases the inflammatory and proliferative signals persist even after wound closure resulting in pathological scars, such as hypertrophic (HTS) and keloid scars. Although most previous studies have considered these scars as dermal phenomena, 11,12 we as well as others have identified abnormalities associated with epidermal keratinocytes in HTS perhaps as a result of aberrant epidermal-mesenchymal interactions. 13,14 One of the most sensitive biochemical markers of terminal differentiation in keratinocytes is the keratin protein family that constitutes the major cytoskeletal architecture of all epithelia. In humans, the family consists of 30 polypeptides (including trichocytic keratins of hair and nail) that are divided into two types; type I is usually acidic and includes K9 to K20; type II is usually basic/neutral and includes K1 to LXR-623 K8. 15,16 Keratins are usually expressed in pairs of type I and type II polypeptides in epithelia and undergo heterotypic association to form filaments. In stratified epithelia the basal keratinocytes express K5, K14, K19 (mucosal epithelia), and K15 as major keratins. 17-19 In the suprabasal compartment the differentiating keratinocytes express different keratin pairs depending on the specific pathway of differentiation, for example, NFAT2 in skin the suprabasal keratinocytes express K1/K10, in buccal epithelia they express K4/K13, and in cornea they express K3/K12. 17 Keratins K6, LXR-623 K16, and K17.