Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus

CD44 is a polymorphic integral membrane glycoprotein that serves as the pri ncipal cell surface receptor for hyaluronate, the major component of the ex tracellular matrix. CD44 is abundantly found in the skin and functions as a cell adhesion molecule. In a recent study we have observed a massive derma l accumulation of hyaluronate as a result of the in vivo selective suppress ion of CD44 in keratinocytes in mice expressing a keratin 5 promoter-driven CD44 anti-sense transgene. As the histologic features of the dorsal skin o f these transgenic mice display some similarities to those of the skin lesi ons of lichen sclerosus et atrophicus, we explored the nature of the materi al accumulated in the dermis of genital and extragenital lesions of 14 pati ents with lichen sclerosus et atrophicus by Alcian Blue and human CD44 rece ptor globulin stainings, as well as the epidermal expression of CD44 protei n and mRNA by immunohistochemistry and in situ hybridization. In this study we provide evidence that hyaluronate is accumulated in the superficial der mis of lichen sclerosus et atrophicus lesions, in particular by the use of human CD44 receptor globulin staining, which binds specifically to hyaluron ate. In addition we show that the protein and mRNA expression of CD44 in th e epidermis of the involved lichen sclerosus et atrophicus skin from genita l and extragenital areas is significantly decreased, and in some cases comp letely lost. In contrast, keratinocyte CD44 expression was unaltered in the skin lesions of lupus erythematosus, scleroderma and reticular erythematou s mucinosis, despite the presence of a mucinous material in the dermis. The se results suggest that a decrease in CD44 in the keratinocytes may be corr elated with an abnormal dermal accumulation of hyaluronate in the lesions o f lichen sclerosus et atrophicus, and may play a pathogenetic role in this disease.