Retinoic acid and hydroquinone induce inverse expression patterns on cornified envelope-associated proteins: Implication in skin irritation

• DEGs on 1q21 locus showed an opposite expression pattern in response to RA and HQ.
• RA-induced irritation reduced expression of cornified envelope-associated proteins.
• HQ-induced irritation increased expression of cornified envelope-associated proteins.
• The opposite expression in response to RA and HQ developed in vitro and in vivo.
• The opposite expression developed in concentrations of varying irritation intensities.

BackgroundHydroquinone (HQ) with or without retinoic acid (RA) is routinely used for the treatment of hyperpigmented conditions. Skin irritation is a major problem with popular depigmenting agents, resulting in postinflammatory hyperpigmentation.ObjectiveTo examine the molecular mechanism associated with skin irritation by RA or HQ.MethodsA genome-wide transcriptional profiling analysis was performed using monolayer cultures of human keratinocytes treated with or without irritant doses of RA, HQ, or sodium lauryl sulfate (SLS), a representative irritant. Differentially expressed genes (DEGs) were mapped on human chromosomes using a Manhattan plot. For the validation of candidate DEGs, the chemicals with different concentrations of varying irritation intensities were applied in vitro and in vivo and analyzed using real time-PCR and Western blotting.ResultsDEGs mapped to the 1q21 locus, which is composed of a cluster of genes encoding the cornified envelope precursors, showed an inverse expression pattern in response to HQ and RA. Concentrations of RA and HQ that induced a broad range of irritant responses in cultured cells or mice skin also induced inverse effects on the expression of cornified envelope-associated proteins.ConclusionsGenetic modulation on cornified envelope-associated proteins by RA-induced irritation, which may be involved in physiological skin barrier disturbance, could be inverse to that by HQ- or SLS-induced irritation.