Diversity of desmosomal proteins in regenerating epidermis: immunohistochemical study using a human skin organ culture model

We recently established a skin organ culture model for epithelial healing b y creating a central defect in freshly excised human skin specimens and kee ping them in culture for up to 7 days, either untreated or with transplanta tion of allogenic or autologous keratinocytes, In this study the molecular diversity of cell-cell junction proteins in the regenerating epidermis was analysed immunohistochemically using a broad spectrum of monoclonal antibod ies against glycoproteins (cadherins) and plaque proteins of desmosomes, At all stages studied the entire set of desmosomal cadherins [desmogleins (Ds g) 1-3 and desmocollins (Dsc) 1-3] was detected, with Dsg3, Dsc2 and Dsc3 b eing the most prominent. In the disordered neoepithelium at day 3 (after tr ansplantation) some desmosomal cadherins appeared in their respective strat um compartments. In regenerating epidermis on day 7, which exhibited a more ordered stratification and a compact horny layer, stratification-related p atterns of desmosomal cadherins were more pronounced. However, some immatur ity of the day-7 neoepidermis was reflected by relatively low levels of the maturation-associated Dsg1 and Dsc1 and a strong basal layer expression of Dsg2 which is sparse in normal epidermis, Desmosomal plaque proteins showe d expression patterns similar to those in normal healthy epidermis, The adh erens junction-related E-cadherin was also detected. Dendritic cells (melan ocytes, Langerhans cells) were mainly present at the wound margins. In conc lusion, this study demonstrated partial but not complete epidermal maturati on and junction development during regeneration up to day 7, This model sho uld also be useful in future studies to evaluate the effects of growth horm ones to be used in therapeutic trials on chronic leg ulcers.