116 Weak Links in the Permeability Barrier of the Skin

Abstract

The microbiota composition and chemical milieu have been shown to prominently differ in topographically distinct healthy skin areas, and recently, our workgroup identified differences in the immune activity of distinct regions as well. As a continuation of our work, we aimed to study the barrier function and compare the expression levels of major permeability barrier components (stratum corneum and tight junction [TJ]) at the molecular level in healthy sebaceous gland-rich (SGR), apocrine gland-rich (AGR), and gland-poor (GP) skin regions. Molecules involved in cornified envelope (CE) formation, desquamation and desmosome formation were investigated in parallel with TJ molecules at the mRNA and protein levels by qRT-PCR and immunohistochemistry. Desmosome and TJ structures were also visualized and quantified by confocal microscopy. While CE structure components were similarly expressed, kallikrein proteases showed significantly higher mRNA levels in SGR and AGR regions compared to GP, and immunohistochemistry indicated their prominent presence in sebaceous and apocrine glands. Desmosome and TJ components’ mRNA levels were similar in the three regions, in contrast, significantly lower protein levels of DSG1, CDSN (desmosome), and OCLN (TJ) molecule were detected in the SGR region, while in AGR skin, the presence of DSG1 (desmosome), OCLN and CLDN1 (TJ) was significantly decreased compared to GP areas. We propose that the increased levels of KLK enzymes and their degradation processes are responsible for the weakened cell junctions in SGR and AGR skin which may explain why certain acantholytic skin disorders (e.g. Darier’s disease, Hailey-Hailey disease) are localized to these areas.