Regional Differences in the Permeability Barrier of the Skin—Implications in Acantholytic Skin Diseases

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).

The Fate of Epidermal Tight Junctions in the stratum corneum: Their Involvement in the Regulation of Desquamation and Phenotypic Expression of Certain Skin Conditions

“…Differences in the epidermal permeability barrier related to body region do occur and are related to SC thickness, pilosity, and the local abundance of secretory glands [51]. Nevertheless, we did not detect any differences between the numbers of TJ remnants observed in abdominal and arm skin, suggesting that similar TJ homeostasis is in play in both these body sites.…”

ACE-2 receptor expression on the back of the hand: Implications in the indirect transmission of SARS-CoV-2

“…In the literature it has been reported that the skin is not uniform, it presents differences in its permeability, activity of the immune system and even its microbial composition. (11). The distribution of sebaceous cells seems to be an important point, since areas rich in sebaceous glands are characterized by weaker permeability barrier characteristics, mainly due to lower expression of tight junction proteins (11).…”

“…(11). The distribution of sebaceous cells seems to be an important point, since areas rich in sebaceous glands are characterized by weaker permeability barrier characteristics, mainly due to lower expression of tight junction proteins (11). It is for this reason that it is important to analyze speci c epithelial regions, which may be more susceptible to SARS-CoV-2 infection or, failing that, be a site of probable transmission; such is the case of the back of the hand.…”