{"title":"Metabolome analyses of skin dialysate: Insights into skin interstitial fluid biomarkers","authors":"Akihiko Oharazawa , Gulinu Maimaituxun , Koichi Watanabe , Takeshi Nishiyasu , Naoto Fujii","doi":"10.1016/j.jdermsci.2024.04.001","DOIUrl":"10.1016/j.jdermsci.2024.04.001","url":null,"abstract":"<div><h3>Background</h3><p>Metabolites in biofluids can serve as biomarkers for diagnosing diseases and monitoring body conditions. Among the available biofluids, interstitial fluid (ISF) in the skin has garnered considerable attention owing to its advantages, which include inability to clot, easy access to the skin, and possibility of incorporating wearable devices. However, the scientific understanding of skin ISF composition is limited.</p></div><div><h3>Objective</h3><p>In this study, we aimed to compare metabolites between skin dialysate containing metabolites from the skin ISF and venous blood (plasma) samples, both collected under resting states.</p></div><div><h3>Methods</h3><p>We collected forearm skin dialysate using intradermal microdialysis alongside venous blood (plasma) samples from 12 healthy young adults. We analyzed these samples using capillary electrophoresis–fourier transform mass spectrometry–based metabolomics (CE–FTMS).</p></div><div><h3>Results</h3><p>Significant positive correlations were observed in 39 metabolites between the skin dialysate and plasma, including creatine (a mitochondrial disease biomarker), 1-methyladenosine (an early detection of cancer biomarker), and trimethylamine N-oxide (a posterior predictor of heart failure biomarker). Based on the Human Metabolome Technologies database, we identified 12 metabolites unique to forearm skin dialysate including nucleic acids, benzoate acids, fatty acids, amino acids, ascorbic acid, 3-methoxy-4-hydroxyphenylethyleneglycol (an Alzheimer’s disease biomarker), and cysteic acid (an acute myocardial infarction biomarker).</p></div><div><h3>Conclusion</h3><p>We show that some venous blood biomarkers may be predicted from skin dialysate or skin ISF, and that these fluids may serve as diagnostic and monitoring tools for health and clinical conditions.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 141-147"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000665/pdfft?md5=8ecc49ad5ecd889243a6e719b14312fe&pid=1-s2.0-S0923181124000665-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Luo , Xiaokai Fang , Yuan Zhou , Yu Zhang , Wei Li , Sean X. Leng , Xu Yao , Xiaochun Liu
{"title":"Senescent fibroblasts and innate immune cell activation might play a role in the pathogenesis of elderly atopic dermatitis","authors":"Yang Luo , Xiaokai Fang , Yuan Zhou , Yu Zhang , Wei Li , Sean X. Leng , Xu Yao , Xiaochun Liu","doi":"10.1016/j.jdermsci.2024.04.002","DOIUrl":"10.1016/j.jdermsci.2024.04.002","url":null,"abstract":"<div><h3>Background</h3><p>Elderly atopic dermatitis (AD) is a subtype of AD defined by age (≥ 60 years). The molecular characteristics of elderly AD remain to be clarified.</p></div><div><h3>Objective</h3><p>We sought to characterize the molecular features of skin lesions and peripheral blood mononuclear cells (PBMCs) in patients with AD across different age, focusing on elderly AD.</p></div><div><h3>Methods</h3><p>Skin and PBMCs samples were used for RNA sequencing. Analysis of differentially expressed genes and gene set variation analysis were performed. Immunofluorescence staining, quantitative real-time PCR (qRT-PCR), flow cytometry and transwell assay were used for validation.</p></div><div><h3>Results</h3><p>Compared with healthy controls, the skin transcriptome of AD patients showed common signatures of AD, like barrier dysfunction and enhanced Th1/Th2/Th17 immune pathways. In PBMCs, the expression of Th1/Th2 response genes was more remarkable in adult AD, while expression of Th17-related genes was significantly higher in childhood AD. The gene modules associated with natural killer (NK) cells were downregulated in elderly AD. In skin lesions, elderly AD exhibited enrichment of macrophages, fibroblasts and senescence-associated secretory phenotype (SASP) related genes. The correlation among fibroblasts, SASP and innate immune cells were revealed by the co-localization of fibroblasts, macrophages and NK cells in the lesions across different age groups. Fibroblasts under inflammation or senescence could induce stronger chemotaxis of macrophages and NK cells.</p></div><div><h3>Conclusion</h3><p>We identified the molecular phenotypes of skin lesions and PBMCs in elderly AD individuals. Fibroblasts, innate immune cells, and SASP might play important roles in the pathogenesis of elderly AD.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 94-103"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140795036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yao Lin , Yu Sun , Wenyi Hou , Xinling Chen , Feng Zhou , QingFang Xu , Yue Zheng
{"title":"FTO-mediated regulation of m6A methylation is closely related to apoptosis induced by repeated UV irradiation","authors":"Yao Lin , Yu Sun , Wenyi Hou , Xinling Chen , Feng Zhou , QingFang Xu , Yue Zheng","doi":"10.1016/j.jdermsci.2024.01.001","DOIUrl":"10.1016/j.jdermsci.2024.01.001","url":null,"abstract":"<div><h3>Background</h3><p>Ultraviolet (UV) damage is closely related to skin photoaging and many skin diseases, including dermatic tumors. N6-methyladenosine (m6A) modification is an important epigenetic regulatory mechanism. However, the role of m6A methylation in apoptosis induced by repeated UV irradiation has not been characterized.</p></div><div><h3>Objective</h3><p>To explore m6A methylation changes and regulatory mechanisms in the repeated UV-induced skin damage process, especially apoptosis.</p></div><div><h3>Methods</h3><p>HaCaT cells and BALB/c-Nu nude mice were exposed to repeated UVB/UVA+UVB irradiation. Colorimetry and flow cytometry were used to measure cellular viability and apoptosis. m6A-modified genes were detected via colorimetry and methylated RNA immunoprecipitation (MeRIP) sequencing. Methyltransferases and demethylases were detected via RT-PCR, western blotting and immunohistochemistry. Transfection of siRNA and plasmid was performed to knock down or overexpress the selected genes.</p></div><div><h3>Results</h3><p>After UVB irradiation, 861 m6A peaks were increased and 425 m6A peaks were decreased in HaCaT cells. The differentially modified genes were enriched in apoptosis-related pathways. The m6A demethylase FTO was decreased in both HaCaT cells and mouse skin after UV damage. Overexpressing FTO could improve cell viability, inhibit apoptosis and decrease RNA-m6A methylation, including LPCAT3-m6A, which increase LPCAT3 expression, cell viability promotion and apoptosis inhibition.</p></div><div><h3>Conclusion</h3><p>Our study identified the cell m6A methylation change lists after repeated UVB irradiation, and revealed that FTO and LPCAT3 play key roles in the m6A methylation pathogenesis of UV-induced skin cell apoptosis. FTO-m6A-LPCAT3 might serve as a novel upstream target for preventing and treating photoaging and UV-induced skin diseases.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 124-132"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139414762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaxi Chen, Yinghan Wang, Wei Dai, Xinyuan Xu, Qingrong Ni , Xiuli Yi, Pan Kang, Jingjing Ma, Lili Wu, Chunying Li, Shuli Li
{"title":"Oxidative stress-induced hypermethylation and low expression of ANXA2R: Novel insights into the dysfunction of melanocytes in vitiligo","authors":"Jiaxi Chen, Yinghan Wang, Wei Dai, Xinyuan Xu, Qingrong Ni , Xiuli Yi, Pan Kang, Jingjing Ma, Lili Wu, Chunying Li, Shuli Li","doi":"10.1016/j.jdermsci.2024.02.009","DOIUrl":"10.1016/j.jdermsci.2024.02.009","url":null,"abstract":"<div><h3>Background</h3><p>Vitiligo is a skin disorder with melanocyte destruction caused by complex interplay between multiple genetic and environmental factors. Recent studies have suggested DNA methylation is involved in the melanocyte damage, but the underlying mechanism remains unknown.</p></div><div><h3>Objective</h3><p>To explore the abnormal DNA methylation patterns in vitiligo lesional and nonlesional skin, and the mechanism of DNA methylation involved in vitiligo pathogenesis.</p></div><div><h3>Methods</h3><p>Initially, the genome-wide aberrant DNA methylation profiles in lesional and nonlesional skin of vitiligo were detect via Illumina methylation EPIC 850k Beadchip. Subsequently, a comprehensive analysis was conduct to investigate the genomic characteristics of differentially methylated regions (DMRs). Furthermore, the effects of key aberrant methylated genes on cell apoptosis and function of both melanocytes and keratinocytes were further identified and validated by western bloting, ELISA, and immunofluorescence.</p></div><div><h3>Results</h3><p>Compared with nonlesional skins, we discovered 79 significantly differentially methylated CpG sites in vitiligo lesions. These DMRs were mainly located in the gene body and the TS1500 region. Annexin A2 receptor (ANXA2R), a crucial gene in cell apoptosis, was hypermethylated in vitiligo lesions. Furthermore, we showed that ANXA2R displayed hypermethylation and low expression levels in both keratinocytes and melanocytes of vitiligo patients, and the hypermethylated-triggered downregulation of ANXA2R under oxidative stress induced melanocyte apoptosis, and inhibited the secretion of stem cell factor (SCF) from keratinocytes thus impaired the survival of melanocytes.</p></div><div><h3>Conclusions</h3><p>Our study illustrates the DNA methylation modification in vitiligo, and further demonstrates the molecular mechanism of hypermethylated ANXA2R in the dysfunction of melanocytes under oxidative stress.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 115-123"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140469638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tam Kurachi, Hironobu Ishimaru, Ryo Tadakuma, Miu Okaue, Akira Koda, Yuhki Ueda, Takaaki Doi
{"title":"Mucopolysaccharide polysulfate increases local skin blood volume through nitric oxide production","authors":"Tam Kurachi, Hironobu Ishimaru, Ryo Tadakuma, Miu Okaue, Akira Koda, Yuhki Ueda, Takaaki Doi","doi":"10.1016/j.jdermsci.2024.05.001","DOIUrl":"10.1016/j.jdermsci.2024.05.001","url":null,"abstract":"<div><h3>Background</h3><p>Mucopolysaccharide polysulfate (MPS) is widely used as an active ingredient in topical preparations for the treatment of asteatosis and blood flow disorders. Although topical MPS products can increase cutaneous blood flow (CBF), the underlying mechanism remains unclear.</p></div><div><h3>Objective</h3><p>In this study, we aimed to elucidate how MPS increases CBF. We investigated the association of nitric oxide (NO), a powerful mediator associated with increased local blood volume, with the blood flow-accelerating action of MPS in mice. In addition, we verified the effects of MPS on NO production in different skin cell types, such as keratinocytes (KCs), endothelial cells (ECs), and dermal fibroblasts (DFs).</p></div><div><h3>Methods</h3><p>We used raster-scanning optoacoustic imaging mesoscopy to observe <em>in vivo</em> changes in the skin blood volume. NO production was determined in each cell using an NO indicator. An enzyme-linked immunoassay was used to measure the phosphorylated nitric oxide synthase (NOS) levels in ECs, DFs, and KCs in the presence or absence of MPS.</p></div><div><h3>Results</h3><p>Topical application of MPS increased the skin blood volume in mice, and this increase was abolished through the addition of NOS inhibitors. MPS promoted the dose-dependent production of NO in various cells, which caused alterations in the phosphorylation state of NOS.</p></div><div><h3>Conclusion</h3><p>Our findings demonstrate that MPS promotes an increase in skin blood volume and NO production in various skin cell types. These results suggest that MPS can potentially accelerate CBF through the NO biosynthesis pathway in different skin cell types.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 133-140"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000823/pdfft?md5=89e4a267488d198e2a9471e26233865b&pid=1-s2.0-S0923181124000823-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141029937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shirin Emtenani , Beke E. Linnemann , Andreas Recke , Anabelle von Georg , Stephanie Goletz , Enno Schmidt , Nina van Beek
{"title":"Anti-BP230 IgE autoantibodies in bullous pemphigoid intraindividually correlate with disease activity","authors":"Shirin Emtenani , Beke E. Linnemann , Andreas Recke , Anabelle von Georg , Stephanie Goletz , Enno Schmidt , Nina van Beek","doi":"10.1016/j.jdermsci.2024.03.009","DOIUrl":"10.1016/j.jdermsci.2024.03.009","url":null,"abstract":"<div><h3>Background</h3><p>Bullous pemphigoid (BP), the most common subepidermal autoimmune blistering disease, is classically defined by the presence of IgG autoantibodies directed against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230 and the predominance of skin lesions. Several studies have addressed the role of anti-BP180 IgE in patients and experimental models, while data on anti-BP230 IgE are scarce.</p></div><div><h3>Objective</h3><p>To assess anti-BP230 IgE level by ELISA in BP sera and to correlate it with disease severity and clinical characteristics.</p></div><div><h3>Methods</h3><p>BP sera underwent anti-BP230 IgE ELISA and Western blotting against human BP230 fragments.</p></div><div><h3>Results</h3><p>We demonstrate that 36/154 (23%) of BP sera were positive for anti-BP230 IgE. Anti-BP230 IgE levels had no correlation with clinical phenotype or disease activity per se. Interestingly, anti-BP230 IgE was significantly associated with disease activity within individuals during the course of the disease. Additionally, anti-BP230 IgE and total IgE levels showed a significant correlation. Notably, anti-BP230 IgG correlated interindividually with disease activity. By Western blotting, the C-terminal domain of BP230 fragments (C2; amino acids 2024–2349 and C3; amino acids 2326–2649), provided the best serological assay for anti-BP230 IgE detection.</p></div><div><h3>Conclusion</h3><p>As a complementary tool, IgE immunoblotting is recommended to obtain an optimal serological diagnosis, particularly in patients with severe disease without IgG reactivity by BP180- or BP230-specific ELISA. Although the detection of serum anti-BP230 IgE is not of major diagnostic significance, it may be relevant for therapeutic decisions, e.g., for anti-IgE-directed treatment, which has been successfully used in case series of BP.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 2","pages":"Pages 64-70"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000550/pdfft?md5=44c4ae5d075f19f0b790f0f27c49e88c&pid=1-s2.0-S0923181124000550-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}