ALL-TRANS-RETINOIC ACID COMPROMISES DESMOSOME EXPRESSION IN HUMAN EPIDERMIS

An undesirable side-effect of retinoid treatment is skin fragility, As desmosomes are important in maintaining the cohesion of epidermal ker atinocytes, we investigated whether all-trans-retinoic acid (RA) compr omises desmosome expression in human epidermis, thereby predisposing s kin to fragility, Solutions containing 0.025% RA, 5% sodium dodecyl su lphate (SDS) as an irritant control, or vehicle alone were applied to three sites on the buttocks of normal volunteers (n = 9). Treated site s were occluded for 4 days, and biopsies taken under local anaesthesia . Cryostat sections were stained with a panel of antibodies to desmoso mal proteins and visualized by immunofluorescence microscopy. Stained sections were randomized and assessed for intensity of staining. The e pidermal thickness of each treated site was quantified by image analys is. Western blots of epidermal desmocollins were quantified by densito metry. RA and SDS treatments significantly, but equivalently, increase d epidermal thickness compared with vehicle, Immunohistochemically, bo th RA and SDS were shown to reduce epidermal staining for desmoplakin, desmoglein 1, plakophilin 1 and desmocollin 3 equally compared with v ehicle-treated skin (P < 0.001). RA produced a greater reduction in de smocollin 1 staining compared with SDS (P < 0.001). Similar reductions in desmocollins were found by Western blot analysis. Reduced desmocol lin expression may indicate compromised desmosomal adhesion, leading t o the skin fragility that results from retinoid treatment.