Barrier function-related genes and proteins have an altered expression in acne-involved skin.

ABSTRACT

BACKGROUND: Acne vulgaris provides a unique disease setting in which a prominent skin inflammation is coupled with the overproduction of lipid-rich sebum. OBJECTIVES: Our goal was to evaluate the expression of barrier molecules in papular acne skin samples obtained from untreated patients and compare those to the results of healthy and of papulopustular rosacea-involved ones at the mRNA and protein levels. In addition, we aimed to assess the effects of various sebum composing lipids on the expression of proteins involved in barrier formation in keratinocytes. METHODS: Available microarray data sets of papular acne and papulopustular rosacea-affected skin samples were re-analysed with a focus on epidermal barrier-related pathways. Immunohistochemistry was performed to detect barrier molecules in the interfollicular regions of human acne and healthy skin samples. Protein levels of barrier-related genes were measured by western blot in samples of HaCaT keratinocytes treated with selected lipids. RESULTS: Meta-analysis of whole transcriptome data sets revealed that barrier-related pathways are significantly affected in acne vulgaris skin samples. While an altered expression of key molecules in maintaining barrier functions such as filaggrin, keratin 1, involucrin, desmoglein 1, kallikrein 5 and 7, was also observed at the protein levels, our data demonstrated that sebum composing lipids may selectively modify the levels of epidermal barrier-related molecules. CONCLUSIONS: Our results suggest that although not as prominently as in the dry papulopustular rosacea skin, the epidermal barrier in the interfollicular region may be damaged also in the lipid-rich skin samples of papular acne. Furthermore, our findings indicating diverse regulatory effects of various sebum lipids on the expression of barrier molecules in keratinocytes suggest, that they may influence the moisturization of the skin as well. Altogether, our findings could have implications in the development of sebum-modulating anti-acne therapies and even in the care of symptom-free skin.