title: Suprabasal expression of epidermal alpha 2 beta 1 and alpha 3 beta 1 integrins in skin treated with topical retinoic acid.
abstract: In normal adult human skin, expression of epidermal integrins is confined to keratinocytes in the basal layer. However, suprabasal expression of alpha 2, alpha 3 and beta 1 integrin subunits is noted in hyperproliferative epidermis in wound repair and psoriasis. In this study, we examined the effect of topical all-trans-retinoic acid (RA), known to induce epidermal hyperplasia, on expression of integrins in human epidermis. Immunostaining of vehicle-treated skin revealed expression of alpha 2, alpha 3 and beta 1, as well as alpha 6 and beta 4 integrin subunits entirely on basal keratinocytes. Topical application of RA (0.1%) for 2 weeks resulted in marked suprabasal expression of alpha 2, alpha 3 and beta 1 integrin subunits, whereas alpha 6 and beta 4 staining remained on basal keratinocytes. Staining for putative ligands of alpha 2 beta 1 and alpha 3 beta 1 integrins, i.e. type IV collagen, laminin-5 and fibronectin, was not detected in the epidermal layer in RA- or vehicle-treated skin. Treatment of HaCaT keratinocytes in culture with RA (1 mumol/L) enhanced alpha 2 and beta 1 mRNA abundance. Furthermore, RA slightly up-regulated the expression of alpha 2, alpha 3 and beta 1 integrin subunits on primary epidermal keratinocytes and HaCaT cells in culture with no effect on cell proliferation. These results provide evidence that RA-elicited epidermal hyperplasia is associated with aberrant suprabasal expression of alpha 2 beta 1 and alpha 3 beta 1 integrins, and that this also involves direct stimulation of keratinocyte integrin expression by RA.
authors.affiliation: Department of Periodontology, Medical Biochemistry and Pathology, University of Turku, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Häkkinen
authors.forename: J
authors.initials: J
authors.lastname: Westermarck
authors.forename: N
authors.initials: N
authors.lastname: Johansson
authors.forename: H
authors.initials: H
authors.lastname: Aho
authors.forename: J
authors.initials: J
authors.lastname: Peltonen
authors.forename: J
authors.initials: J
authors.lastname: Heino
authors.forename: V M
authors.initials: VM
authors.lastname: Kähäri
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007641:Keratolytic Agents / Q000494:pharmacology*; D008297:Male; D038981:Receptors, Collagen; D017474:Receptors, Laminin / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D039201:Integrin alpha3beta1; D016023:Integrins; D007641:Keratolytic Agents; D038981:Receptors, Collagen; D017474:Receptors, Laminin; D014212:Tretinoin