Regional Differences in the Permeability Barrier of the Skin-Implications in Acantholytic Skin Diseases.

Anikó Kapitány,Andrea Szegedi,Adrienn Jenei,Orsolya Somogyi,Zoltán Hendrik,Barbara Medgyesi,Lilla Szabó,Klaudia Dócs,Zsolt Dajnoki,Gábor Méhes,Péter Szücs,Krisztián Gáspár

doi:10.3390/ijms221910428

Anikó Kapitány, Andrea Szegedi + Show 10 more

Open Access

https://doi.org/10.3390/ijms221910428

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Abstract

The chemical milieu, microbiota composition, and immune activity show prominent differences in distinct healthy skin areas. The objective of the current study was to compare the major permeability barrier components (stratum corneum and tight junction (TJ)), investigate the distribution of (corneo)desmosomes and TJs, and measure barrier function 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 (corneo)desmosome and TJ organization were investigated at the mRNA and protein levels using qRT-PCR and immunohistochemistry. The distribution of junction structures was visualized using confocal microscopy. Transepidermal water loss (TEWL) functional measurements were also performed. CE intracellular structural components were similarly expressed in gland-rich (SGR and AGR) and GP areas. In contrast, significantly lower extracellular protein levels of (corneo)desmosomes (DSG1 and CDSN) and TJs (OCLN and CLDN1) were detected in SGR/AGR areas compared to GP areas. In parallel, kallikrein proteases were significantly higher in gland-rich regions. Moreover, gland-rich areas were characterized by prominently disorganized junction structures ((corneo)desmosomes and TJs) and significantly higher TEWL levels compared to GP skin, which exhibited a regular distribution of junction structures. According to our findings, the permeability barrier of our skin is not uniform. Gland-rich areas are characterized by weaker permeability barrier features compared with GP regions. These findings have important clinical relevance and may explain the preferred localization of acantholytic skin diseases on gland-rich skin regions (e.g., Pemphigus foliaceus, Darier’s disease, and Hailey–Hailey disease).

Highlights

The density and size of hair follicles and sebaceous, eccrine, and apocrine glands are different across skin areas, creating a diverse environment for microbiota [1]
We aimed to investigate the two major permeability barrier elements, the stratum corneum (SC) and the tight junctions (TJ), at the mRNA and protein levels [11,12]
sebaceous gland-rich (SGR) and apocrine gland-rich (AGR) regions were characterized by significantly higher Transepidermal water loss (TEWL) levels compared to GP areas, indicating differences in barrier function among healthy skin regions

Summary

Introduction

The density and size of hair follicles and sebaceous, eccrine, and apocrine glands are different across skin areas, creating a diverse environment for microbiota [1]. In parallel with the physiological properties and chemical milieu [1], the microbiota composition varies in topographically different skin areas [2]. Significantly different epidermal levels of antimicrobial peptides (AMPs) and chemokines and distinct numbers of dermal T cells and dendritic cells are observed in different skin regions [4,5,6]. In sebaceous (sebaceous gland-rich (SGR)) and moist (apocrine gland-rich (AGR)) skin regions, AMPs are 2- to 40-fold upregulated at the mRNA level and 4- to 9-fold increased at the protein level compared to dry (gland-poor (GP)) skin areas [4,5]. The antimicrobial barrier of the skin cannot be considered uniform

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