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Aim: Senescence‐accelerated mouse prone (SAMP) mice can reproduce the same conditions as normal aging mice in a short period. Although SAMP mice have been widely used in aging research, research on skin function in SAMP mice is lacking. In this study, to investigate the skin function of SAMP mice, we analyzed the expression of genes important for maintaining skin function. Methods: Eight‐month‐old SAMP mice and senescence‐accelerated mouse resistant (SAMR) mice with normal aging were used. The expression levels of various functional genes in the skin were analyzed. Results: The dermal water content of SAMP mice was significantly lower than that of SAMR mice, indicating dry skin. The mRNA expression levels of elastin (Ela), filaggrin (Flg), loricrin (Lor), collagen type I alpha 1 chain (Col1a1) and Col1a2 in the skin of SAMP mice were all significantly decreased compared with those of SAMR mice. Hyaluronan‐degrading enzyme (Hyal1) expression levels in SAMP mice were similar to those in SAMR mice, but hyaluronan synthase (Has2) levels were significantly decreased. In addition, the expression level of aquaporin‐3 in the skin of SAMP mice was significantly decreased at both the mRNA and protein levels. Conclusions: In the skin of SAMP mice, the expression levels of various skin function‐regulating genes were decreased, and this phenomenon might cause skin dryness. The SAMP mouse could be a tool for analyzing skin aging. Geriatr Gerontol Int 2023; 23: 951–957. [ABSTRACT FROM AUTHOR]

Background: The association between pet exposure in infancy, early childhood eczema, and FLG mutations remains unclear., Methods: This was a birth cohort study performed in Tokyo, Japan. The primary outcome was current eczema based on questionnaire responses collected repeatedly from birth to 5 years of age. Generalized estimating equations and generalized linear modeling were used to evaluate the association., Results: Data from 1448 participants were used for analyses. Household dog ownership during gestation, early infancy, and 18 months of age significantly reduced the risk of current eczema. Household cat ownership also reduced the risk of current eczema, albeit without statistical significance. The combined evaluation of children from households with pets, be it cats, dogs or both, the risk of current eczema at 1-5 years of age was lower in those with household pet exposure ownership during gestation (RR = 0.59, 95 % CI 0.45-0.77) and at 6 months (RR = 0.49, 95 % CI 0.36-0.68). , Reduced risks of eczema were also observed at 2-5 (RR = 0.52, 95 % CI 0.37-0.73) and 3-5 years of age (RR = 0.50 95 % CI 0.35-0.74) when the respective household pet ownership were evaluated at 18 months and 3 years of age. These protective associations of reduced risk of eczema were only observed in children without FLG mutations., Conclusions: Household dog and pet (dog, cat, or both) ownership was protective against early childhood eczema in a birth cohort dataset. This protective association was observed only in children without FLG mutations, which should be confirmed in studies with larger cohorts., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background and Objective Keratinization of the oral mucosa, such as the gingiva, has been shown to be important for periodontal health. Caspase-14 is a protease that plays a role in keratinization of the epidermis. The objective of this study was to investigate whether the expression of caspase-14 is intimately linked with keratinization and to examine the effect of the main component of green tea on the improvement of keratinization in rat oral mucosal preparations. Material and Methods Histological and immunohistochemical analyses and quantitative mRNA measurements of caspase-14 and its substrate filaggrin were performed using different types of rat epithelial tissue and organotypic reconstruction culture models derived from epithelial cells and fibroblasts taken from the rat oral mucosa. Results In the skin, palate, buccal mucosa and esophagus, the degree of keratinization appeared to be associated with expression of cytokeratin 10. The relative protein and mRNA expression levels of caspase-14 and filaggrin were consistent with the degree of keratinization in the following order: skin > palate > buccal mucosa > esophagus. The culture models of palatal and buccal mucosa retained a stratified epithelial structure. Expression of caspase-14 appeared to be stronger in the palatal model than in the buccal model. Remarkably, epigallocatechin-3-gallate (EGCG) improved the localization of cytokeratins and increased the expression of caspase-14 and filaggrin. This expression was more intense in the palatal model than in the buccal model, indicating that both models maintain the intrinsic properties of keratinization of the mucosa from where the cultured cells were derived. Conclusions These results suggest that keratinization is closely associated with expression of caspase-14 and filaggrin. Our reconstruction models are promising tools for drug evaluation and show that EGCG is beneficial for improving both keratinization and expression of the linked protease in the oral mucosa. [ABSTRACT FROM AUTHOR]

Background: Filaggrin is a key protein involved in skin barrier function. Recently, mutations in the filaggrin gene, FLG, were identified in European families with ichthyosis vulgaris (IV) and shown to be an important predisposing factor for atopic dermatitis (AD). Objective: To study the role of FLG mutations in IV/AD in Japan. Methods: The known filaggrin mutations were studied by genotyping and new mutations identified by DNA sequencing. Results: The European-specific mutations R501X and 2282del4 were absent from 253 Japanese individuals. We therefore sequenced the FLG gene in 4 Japanese families with IV and identified 2 novel mutations, 3321delA and S2554X. Immunohistologic and ultrastructural observations indicated that both truncation mutations lead to a striking reduction of keratohyalin granules in the epidermis. We screened 143 Japanese patients with AD for these FLG null mutations and identified them in 8 patients with AD (5.6%), including S2554X in 6 patients (4.2%) and 3321delA in 2 patients (1.4%). Both null variants were absent from 156 unrelated Japanese nonatopic and nonichthyotic controls, giving a significant statistical association between the FLG mutations and AD (χ2 P value, .0015). This is the first report of FLG mutations in a non-European population. Conclusion: Our data indicate that FLG mutations in Japan are unique from those found in European-origin populations. Clinical implications: Filaggrin null variants are also significant predisposing factors for AD in Japan and, on the basis of the recent European studies, may predict a more severe and persistent form of atopy. [Copyright &y& Elsevier]

Background and Aim: Exposure to phthalates and phosphorus flame retardants (PFRs) is considered to be a risk factor for asthma and allergies. However, little is known about the contribution of loss-of-function mutations in the gene encoding filaggrin (FLG) gene, which are considered to be predisposing factors for eczema and asthma, to these associations. We investigated the associations between exposure to phthalates and PFRs in dust and eczema/wheeze among Japanese children, taking into consideration loss-of-function mutations in FLG., Methods: This study was part of the Hokkaido study on Environment and Children's Health. Seven phthalates and 11 PFRs in household dust were measured by gas chromatography-mass spectrometry. Eczema and wheeze were assessed in children aged 7 years using the International Study of Asthma and Allergies in Childhood questionnaire. Eight FLG mutations previously identified in the Japanese population were extracted from cord blood samples. Children with one or more FLG mutations were considered to be positive for FLG mutations. The study included 296 children who had complete data (birth records, FLG mutations, first trimester and 7 years questionnaires, and phthalate/PFR levels). Odds ratios (ORs) and 95% confidential intervals (CIs) of eczema and wheeze were calculated for log-transformed phthalate/PFR levels by logistic regression. We also performed stratified analyses based on FLG mutations., Results: The prevalence rates of eczema and wheeze were 20.6% and 13.9%, respectively. Among children without any FLG mutations, tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) increased the OR of wheeze, (OR: 1.22, CI: 1.00-1.48). Significant p values for trends were found between tris (2-butoxyethyl) phosphate (TBOEP) and eczema and di-iso-nonyl phthalate (DiNP) and eczema among children without any FLG mutations, respectively., Conclusions: Despite our limited sample size and cross-sectional study design, the effects of indoor environmental factors on childhood eczema and wheeze were clearer in children without loss-of-function mutations in FLG than in children with mutations. Children with FLG mutations might already be cared for differently in terms of medication or parental lifestyle. Further studies in larger populations are warranted so that severity of symptoms and combinations of FLG mutations can be investigated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Mutations in FLG coding profilaggrin cause ichthyosis vulgaris and are an important predisposing factor for atopic dermatitis. Until now, most case-control studies and population-based screenings have been performed only for prevalent mutations. In this study, we established a high-throughput FLG mutation detection system by real-time PCR with a set of two double-dye probes and conducted comprehensive screening for almost all of the Japanese-population-specific FLG mutations (ten FLG mutations). The present comprehensive screening for all ten FLG mutations provided a more precise prevalence rate for FLG mutations (11.1%, n = 820), which seemed high compared with data of previous reports based on screening for limited numbers of FLG mutations. Our comprehensive screening suggested that population-specific FLG mutations may be a significant predisposing factor for hay fever (odds ratio = 2.01 [95% CI: 1.027-3.936, P < 0.05]), although the sample sizes of this study were too small for reliable subphenotype analysis on the association between FLG mutations and hay fever in the eczema patients and the noneczema individuals, and it is not clear whether the association between FLG mutations and hay fever is due to the close association between FLG mutations and hay fever patients with eczema., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)