“…All-trans retinoic acid (tRA) is the major biologically active metabolite of vitamin A. tRA and related synthetic retinoids have been used widely in the therapy of several skin disorders, including acne (Pedace and Stoughton, 1971), photo-aged skin (Kligman et al, 1984), and psoriasis (Goldfarb et al, 1988). However, the effects of retinoids are often conflicting: retinoids can either stimulate or inhibit cell proliferation depending on the cell type affected or on the conditions used in cell cultivation (Amos and Lotan, 1990;Fisher and Voorhees, 1996;Rogers, 1997;Varani et al, 1989Varani et al, , 1991. Although the mechanism by which retinoids regulate the proliferation of epidermal cells is not completely understood, it has been shown that treatment of normal adult human skin and keratinocytes with tRA not only leads to thickening of the skin but also induces significant expression of several genes including HB-EGF (Bernard et al, 2002;Stoll and Elder, 1998;Varani et al, 2001).…”