IN-VIVO MODULATION OF CONNEXIN-43 AND CONNEXIN-26 OF HUMAN EPIDERMIS BY TOPICAL RETINOIC ACID TREATMENT

After 14 weeks of topical application of 0.1% all-trans-retinoic acid to the napes of volunteers, we observed a 2.5-fold increase in the thi ckness of epidermis, owing to an increase (p<0.001) in the number and size of keratinocytes and the induction of keratin 6. These changes in the differentiation of epidermal keratinocytes were paralleled by an increase in the amount of Cx43, a connexin that is normally expressed in human epidermis, and by the massive induction of Cx26, which is bar ely detectable in normal interfollicular epidermis, as judged at both the transcript (Northern blotting) and the protein level (immunolabeli ng). In contrast, retinoic acid treatment did not after the morphology and connexin pattern of hair follicles or of sebaceous and sweat glan ds, and did not induce the expression of other connexins (C32, Cx37, C x40) in either skin adnexae or epidermis. These observations suggest t hat the expression of two distinct connexins by interfollicular kerati nocytes is related to selective changes in the differentiation program of epidermis that are induced by retinoic acid.