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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Retinoids reduce formation of keratin aggregates in heat-stressed immortalized keratinocytes from an epidermolytic ichthyosis patient with a KRT10 mutation*.
Acta Dermato-venereologica 2013 January
Epidermolytic ichthyosis (EI) is an autosomal dominant epidermal skin fragility disorder caused by mutations in keratin 1 and 10 (K1 and K10) genes. Mutated keratins form characteristic aggregates in vivo and in vitro. Some patients benefit from retinoid therapy, although the mechanism is not fully understood. Our aim was to demonstrate whether retinoids affect the formation of keratin aggregates in immortalized EI cells in vitro. EI keratinocytes were seeded on cover slips, pre-treated or not with retinoids, heat-stressed, and keratin aggregate formation monitored. K10 aggregates were detected in 5% of cells in the resting state, whereas heat stress increased this proportion to 25%. When cells were pre-incubated with all-trans-retinoic acid (ATRA) or retinoic acid receptor (RAR)-α agonists the aggregates decreased in a dose-dependent manner. Furthermore, ATRA decreased the KRT10 transcripts 200-fold as well as diminished the ratio of mutant to wild-type transcripts from 0.41 to 0.35, thus providing a plausible rational for retinoid therapy of EI due to K10 mutations.
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