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The influences of chronic UVB exposure on epidermal differentiation have been poorly studied compared to dermal photo-aging although those effects are very important in terms of photo-damage to the skin. The purpose of this study was to investigate the effects of chronic UVB exposure on keratin expression in the epidermis. The effects on murine skin of chronic exposure to weak UVB (below 1 MED) was examined by immunoblotting for keratins K10, K5, K6, and K16, by immunohistochemistry using antibodies to K6, K16, and Ki67 as well as by conventional HE staining of skin sections. Alterations of keratin expression induced by the chronic UVB exposure were distinct from those elicited by a single acute UVB exposure. The expression of keratins K6 and K16 was quite long-lasting, continuing for 7 weeks after 6 weeks of chronic UVB exposure and for 6 weeks after 9 weeks of chronic UVB exposure. In contrast, K6 and K16 expression induced by a single UVB exposure at 0.5 MED or 3 MED almost ceased within 2 weeks after that exposure. Furthermore, the expression of the constructive keratins, K5 and K10, remained almost unchanged by chronic UVB exposure. Epidermal thickness was increased significantly immediately after the 9 weeks of chronic UVB exposure; however, it had returned to normal level 6 weeks later. The alterations in keratin expression accompanied the marked disruption of the ordered ultrastructure of keratin intermediate filaments, which were observed by TEM. Thus, chronic exposure to UVB has a deep impact on the biosynthetic regulation of different keratins in the epidermis, thereby interfering with the ordered ultrastructure of keratin intermediate filaments. Those events could have relevance to the mechanism of photo-damage, such as fine wrinkles observed in chronically UV-exposed skin in addition to dermal photo-aging.

Background Specimens for analysing the molecular pathology of skin disease are generally obtained through invasive methods, such as biopsy. However, less burdensome methods are desirable for paediatric patients. We recently established a method that comprehensively analyses RNA present in sebum (skin surface lipid–RNAs: SSL‐RNAs) using a next‐generation sequencer. Using this method, biological information can be obtained from the skin in a completely non‐invasive manner. Objectives To verify the applicability of the SSL‐RNA method for analysis of paediatric skin and analyse the molecular pathology of mild‐to‐moderate atopic dermatitis (AD) in children. Methods We collected sebum specimens from the whole faces of 23 healthy children and 16 children with mild‐to‐moderate AD (eczema area and severity index (EASI) score: 5.9 ± 2.6) ranging in age from 6 months to 5 years, using an oil‐blotting film. We then extracted SSL‐RNAs from the samples and performed an AmpliSeq transcriptomic analysis. Results The expressions of genes related to keratinization (LCE, PSORS1C2, IVL and KRT17), triglyceride synthesis and storage (PLIN2, DGAT2 and CIDEA), wax synthesis (FAR2), ceramide synthesis (GBA2, SMPD3 and SPTLC3), antimicrobial peptides (DEFB1) and intercellular adhesion (CDSN), all of which are related to the skin barrier, are lower in children with AD than in healthy children. The children with AD also have higher expression of CCL17, a Th2‐cytokine and an increased Th2‐immune response as demonstrated by a gene set variation analysis. Moreover, KRT17 and CCL17 expression levels are significantly correlated with the EASI score. Conclusions Molecular changes associated with abnormal immune responses and the epidermal barrier in children with mild‐to‐moderate AD can be determined using the SSL‐RNA method. This non‐invasive method could therefore be a useful means for understanding the molecular pathology of paediatric AD.

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Background:The molecular pathogenesis of atopic dermatitis (AD), presenting skin barrier dysfunction and abnormal inflammations around 1-2 months, is unreported. Objective: We aimed to examine the molecular pathogenesis of very early-onset AD by skin surface lipid-RNA (SSL-RNA) using a non-invasive technology in infants aged 1 and 2 months from a prospective cohort. Methods: We collected sebum by oil-blotting film of infants aged 1 and 2 months and analysed RNAs in their sebum. We diagnosed AD according to the United Kingdom Working Party's criteria. Results: Infants with AD aged 1 month showed lower expression of genes related to various lipid metabolism and synthesis, antimicrobial peptides, tight junctions, desmosomes and keratinization. They also had higher expression of several genes involved in Th2-, Th17-and Th22-type immune responses and lower expression of negative regulators of inflammation. In addition, gene expressions related to innate immunity were higher in AD infants. Infants aged 1 month with neonatal acne and diagnosed with AD aged 2 months already had gene expression patterns similar to AD aged 1 month in terms of redox, lipid synthesis, metabolism and barrier-related gene expression. Conclusion:We identified molecular changes in barrier function and inflammatory markers that characterize the pathophysiology of AD in infants aged 1 month. We also revealed that neonatal acne at 1 month could predict the subsequent development of AD by sebum transcriptome data.