Experimental Dermatology最新文献

{"title":"Circadian Clock Regulates Epidermal Endocrine System in Homeostatic Skin Pigmentation","authors":"Anya Zhu,&nbsp;Lingli Yang,&nbsp;Sylvia Lai,&nbsp;Fei Yang,&nbsp;Daisuke Tsuruta,&nbsp;Ichiro Katayama","doi":"10.1111/exd.70296","DOIUrl":"10.1111/exd.70296","url":null,"abstract":"<p>The circadian clock regulates multiple physiological processes in the skin, including local hormone synthesis and pigmentation. However, how circadian regulation interacts with epidermal endocrine signalling in melanocytes remains unclear. In this study, we investigated whether core circadian regulators influence melanogenesis in human melanocytes and explored their potential link to epidermal endocrine factors and pigmentary disease. Primary normal human epidermal melanocytes were analysed following siRNA-mediated knockdown of the core clock genes basic helix–loop–helix ARNT-like protein 1 (BMAL1) and CLOCK circadian regulator (CLOCK). Silencing either gene significantly reduced melanin synthesis and altered the expression of hormone-related factors. Notably, expression of the vitamin D-metabolizing enzyme CYP27A1 was markedly decreased after BMAL1 or CLOCK knockdown, changes that were associated with reduced melanogenic activity. Consistently, immunohistochemical analysis revealed diminished CYP27A1 expression in melanocytes within vitiligo lesions. These findings demonstrate that disruption of circadian clock regulators impairs melanogenesis and is accompanied by alterations in vitamin D-related components. Our results suggest that circadian regulation may modulate pigmentation partly through effects on vitamin D metabolism, providing new insight into the mechanisms underlying pigmentary disorders.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Type I Interferonopathies and the Development of Cutaneous Sarcoidosis, Morphea, Lichen Planus and Granuloma Annulare: A Retrospective Cohort Study","authors":"Brandon Block,&nbsp;Jaanvi Mehta,&nbsp;Gabriela Soto-Canetti,&nbsp;Alice Tang,&nbsp;Riley Spingler,&nbsp;Benjamin Ungar,&nbsp;Jordan Talia","doi":"10.1111/exd.70295","DOIUrl":"10.1111/exd.70295","url":null,"abstract":"<div>\u0000 \u0000 <p>Dysregulated type I interferon (IFN-I) signalling is implicated in the pathogenesis of several systemic autoimmune conditions, collectively termed type I interferonopathies. Emerging evidence suggests that aberrant IFN-I pathway activity may similarly contribute to certain autoimmune dermatoses, namely granuloma annulare (GA), lichen planus (LP), cutaneous sarcoidosis (CS) and morphea. We sought to investigate this association using large, real-world cohorts, with type I interferonopathies serving as proxies for IFN-I-driven inflammation. Four retrospective cohort studies were conducted in parallel using the TriNetX Global Collaborative Network. Patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren's disease (SjD) and dermatomyositis (DM) were 1:1 propensity score-matched to healthy controls (HCs), and relative risks (RRs) for developing GA, CS, LP and morphea were calculated. Sensitivity analyses compared each interferonopathy cohort to patients with gout and ankylosing spondylitis, rheumatologic conditions not mediated by IFN-I pathways. Increased risk of morphea and LP was observed across all four interferonopathy cohorts relative to HCs. Patients with SLE, SSc and SjD had an increased risk of developing CS. GA risk was significantly increased only among patients with SLE and DM. Sensitivity analyses were broadly corroborative. These findings reveal consistent associations between type I interferonopathies and subsequent development of LP, CS and morphea. The results of these analyses are hypothesis-generating and complement existing evidence of an IFN-I mediated pathogenesis for these dermatoses. Prospective studies employing large, representative cohorts paired with transcriptomic and proteomic technologies for mechanistic confirmation are warranted.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"So Much More Than Just Structural Support: Laminin-332 and Its Multifaceted Functions in Skin Homeostasis and Disease","authors":"Piotr Parzymies","doi":"10.1111/exd.70293","DOIUrl":"10.1111/exd.70293","url":null,"abstract":"<p>The extracellular matrix (ECM) is increasingly recognised as a dynamic regulator of tissue function beyond its traditional structural role. In the skin, the ECM supports tissue integrity while also controlling processes such as stem cell maintenance, wound healing and disease progression. This review focuses on laminin-332, a key component of the epidermal–dermal junction. Its essential role in maintaining epidermal cohesion is illustrated by junctional epidermolysis bullosa, a severe inherited blistering disorder and recent advances in laminin-332-targeted genetic therapies are discussed. Beyond structural support, laminin-332 also mediates signalling through integrins and syndecans, thereby influencing epidermal homeostasis, migration, repair and the development of cutaneous squamous cell carcinoma. Its role in epidermal stem cell maintenance further links laminin-332 to skin ageing. The review also examines its functions in hair follicle biology, melanocyte behaviour, skin immunity and emerging evidence implicating laminin-332 in epidermal metabolism—an exciting area for future investigation. Finally, the structure and functions of other cutaneous laminins are compared with laminin-332 to help explain its specialised roles.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TEAD4 Drives SKCM Progression Through COL1A2 Transcriptional Activation and Modulation of AKT/mTOR Signalling and Necroptosis-Related Phenotypes","authors":"Jiaqiong Lin,&nbsp;Yingchun Zheng,&nbsp;Zongrui Shen,&nbsp;Qian Liu,&nbsp;Fangkeng Liang,&nbsp;Fei He,&nbsp;Xiaoyong Li,&nbsp;Fu Xiong","doi":"10.1111/exd.70288","DOIUrl":"https://doi.org/10.1111/exd.70288","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin cutaneous melanoma (SKCM) continues to pose significant therapeutic challenges owing to its aggressive nature and evolving resistance mechanisms. This study investigates the under-characterized role of Hippo pathway effector TEAD4 in SKCM pathogenesis through integrated multiomics analysis of clinical cohorts (TCGA, GEO, immunotherapy cohorts) combined with functional validation in A375 cell models and xenograft systems. Our pan-cancer analysis identified TEAD4 overexpression as a strong prognostic indicator associated with poor survival and a potential association with inferior immunotherapy response. Functional experiments in A375 cells and xenograft models showed that TEAD4 knockdown impaired proliferation, migration and tumour growth while increasing necroptosis-related markers. Mechanistic investigation showed that TEAD4 directly binds the COL1A2 promoter and promotes its transcription. In A375 cells, COL1A2 overexpression attenuated TEAD4 knockdown-induced changes in AKT/mTOR signalling, necroptosis-related markers and malignant phenotypes. These findings support a TEAD4 and COL1A2 regulatory model associated with SKCM progression, AKT/mTOR pathway activity and necroptosis-related phenotypes, and suggest TEAD4 as a prognostic factor and potential biomarker associated with immunotherapy outcome that requires further validation.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Objective Wound Edge Classification in Clinical Practice","authors":"Corrado Zengarini,&nbsp;Tommaso Giacometti,&nbsp;Yuri Merli,&nbsp;Davide Griffa,&nbsp;Luca Rapparini,&nbsp;Alessio Natale,&nbsp;Michele Fruci,&nbsp;Gastone Castellani,&nbsp;Daniel Remondini,&nbsp;Michelangelo La Placa,&nbsp;Alessandro Pileri,&nbsp;Michela Starace,&nbsp;Nico Curti","doi":"10.1111/exd.70287","DOIUrl":"https://doi.org/10.1111/exd.70287","url":null,"abstract":"<p>Wound edge assessment is a key component of chronic wound evaluation, but it remains highly subjective and affected by inter-observer variability, particularly when performed on two-dimensional clinical photographs. We retrospectively analysed 1 860 wound images acquired during routine clinical practice and independently annotated by four expert clinicians. An automated image-analysis pipeline was used to segment the wound, standardise the peri-wound border region, and estimate the three-dimensional profile of the wound edge. We first tested whether geometry-derived edge profiles alone could reproduce clinical wound edge categories. We then evaluated whether adding global visual descriptors of wound shape, colour appearance, and surface pattern improved agreement with clinicians. Inter-clinician agreement was low, confirming the intrinsic subjectivity of wound edge classification. Geometry-based analysis identified coherent edge-profile patterns but showed poor correspondence with clinical annotations. In contrast, a supervised classifier incorporating both geometric and visual features achieved agreement comparable to, and in some comparisons higher than, the agreement observed among clinicians. Clinical wound edge assessment is not driven by edge geometry alone. Visual cues such as wound shape, colour appearance, and surface pattern appear to influence expert classification and may contribute to variability. Automated image-based analysis may support more reproducible wound edge assessment, provided that it is externally validated in diverse clinical settings.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When the Niche Loses Contrast: Mechanical Erosion of the Epidermal Stem Cell Compartment in Aging Skin","authors":"Sang Eun Lee,&nbsp;Dong Hun Lee","doi":"10.1111/exd.70292","DOIUrl":"10.1111/exd.70292","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold Stress Activates ACSL1+ Macrophages in a Fatty Acid-Dependent Manner to Exacerbate Psoriasis","authors":"Ce Shuai,&nbsp;Qinyi Ge,&nbsp;Li Zhang,&nbsp;Han Cao,&nbsp;Haoying Chen,&nbsp;Szeman Cheung,&nbsp;Youcong Wang,&nbsp;Lihong Chen,&nbsp;Yongyong Yuan,&nbsp;Xia Li,&nbsp;Jie Zheng,&nbsp;Feng Xue","doi":"10.1111/exd.70280","DOIUrl":"10.1111/exd.70280","url":null,"abstract":"<div>\u0000 \u0000 <p>The relapse of psoriasis precludes a complete cure and can result in multisystem comorbidities, making relapse prevention a critical clinical challenge. Clinically, psoriasis tends to worsen or relapse in winter, but the underlying mechanisms remain unclear. In this study, we utilized an imiquimod (IMQ)-induced psoriasis-like mouse model to investigate the role of cold stress in the exacerbation of psoriasis during winter. Our data indicate that cold stress significantly aggravates IMQ-induced psoriatic lesions. While cold stress alone does not directly induce psoriasis, it can promote the development of psoriasis-like lesions in mice exposed to low doses of IMQ. Single-nucleus transcriptome analysis demonstrated that cold stress leads to the remodelling of macrophage phenotypes in psoriatic lesions, with a notable increase in ACSL1+ macrophages. These cells exhibit higher intracellular neutral lipid content and produce more IL-1β, which in turn stimulates γδT cells to secrete more IL-17A. The increase of ACSL1+ macrophages is associated with cold stress–induced lipid synthesis in dermal adipocytes. Notably, the number of ACSL1+ IL-1β + macrophages is significantly increased in the skin of psoriasis patients in winter. Therefore, targeting the formation of ACSL1+ macrophages may be a potential strategy to prevent the worsening of psoriasis in winter.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin, AhR and UVR Photoprotection: Distinguishing Broad-Spectrum Injury Attenuation From Solar-Relevant AhR Modulation.","authors":"Haohao Wan, Gen Quan","doi":"10.1111/exd.70294","DOIUrl":"https://doi.org/10.1111/exd.70294","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":"e70294"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Polyamine Metabolism-Related Biomarkers in Psoriasis: A Study Based on Transcriptomics and Single-Cell Sequencing","authors":"Li Zhang,&nbsp;Xiaoqiang Jia,&nbsp;Xia Liu,&nbsp;Yanni Yang","doi":"10.1111/exd.70289","DOIUrl":"10.1111/exd.70289","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis (PS) is linked to altered polyamine metabolism, which may drive chronic inflammation and abnormal keratinocyte proliferation. We integrated transcriptomics and single-cell RNA sequencing (scRNA-seq) to identify polyamine metabolism-related genes (PMRGs) as biomarkers for PS and elucidate their mechanisms. Through the application of differential expression analysis, three machine learning algorithms, combined with receiver operating characteristic (ROC) analysis and expression quantification, biomarkers related to polyamine metabolism in PS were identified. Furthermore, the expression of these biomarkers was verified through western blotting. These biomarkers were subsequently incorporated into a diagnostic nomogram. Further investigations of these biomarkers included enrichment analysis and immune infiltration analysis. Additionally, scRNA-seq analysis was conducted to annotate the cell types in PS, providing insights into the cellular mechanisms underlying the progression of PS. In PS samples, biomarkers PSME2, PSMB5, PSMC4, PSMB10 and SMOX were significantly upregulated, achieving an area under the ROC curve (AUC) &gt; 0.9 in GSE13355. Western blotting confirmed their upregulation, aligning with bioinformatics results. These biomarkers were closely associated with inflammation, cell proliferation, energy metabolism and signalling pathways. scRNA-seq identified 11 cell types, with mature dendritic cell (mDC) showing notable proportional differences between PS patients and controls, marking them as key cells. mDC exhibited distinct developmental trajectories with branching heterogeneity, featuring a reduction in early stages and an increase in later stages. Biomarker expression levels were higher in the later stages of mDC differentiation. The five PMRGs—PSME2, PSMB5, PSMC4, PSMB10 and SMOX—identified through comprehensive analyses, emerged as significant biomarkers for PS, providing promising diagnostic targets and mechanistic insights for the early detection and targeted treatment of PS.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OPN1SW Modulates UVB-Associated DHCR7 Reduction and Associated 25(OH)D3 and Sterol-Pool Responses in Keratinocytes","authors":"Yating Yang,&nbsp;Wen Zeng,&nbsp;Guangsu Chen,&nbsp;Wei Zhang,&nbsp;Yushen Su,&nbsp;Hongguang Lu","doi":"10.1111/exd.70285","DOIUrl":"10.1111/exd.70285","url":null,"abstract":"<div>\u0000 \u0000 <p>Ultraviolet B (UVB) irradiation initiates cutaneous vitamin D-related photochemistry from 7-dehydrocholesterol (7-DHC), which is also the immediate precursor of cholesterol via 7-dehydrocholesterol reductase (DHCR7). Thus, DHCR7 occupies a branch-point position linking cholesterol biosynthesis and UVB-associated vitamin D-related metabolism. How keratinocytes regulate this metabolic relationship under UVB remains unclear. We examined whether OPN1SW is associated with DHCR7 protein abundance, conditioned medium 25-hydroxyvitamin D3 [25(OH)D3] (a vitamin D-related readout) and sterol-pool responses in UVB-exposed keratinocytes. A UVB dose that preserved &gt; 80% cell viability, 10 mJ/cm², increased OPN1SW protein abundance and reduced DHCR7 protein abundance in human epidermal keratinocytes and HaCaT cells. These changes were accompanied by increased conditioned medium 25(OH)D3 and a reduced cellular sterol-pool readout. OPN1SW overexpression increased DHCR7 protein abundance under basal conditions. Under UVB exposure, OPN1SW overexpression attenuated UVB-associated DHCR7 reduction, attenuated the UVB-associated increase in conditioned medium 25(OH)D3 and partially preserved the sterol-pool readout. Conversely, OPN1SW knockdown exacerbated DHCR7 reduction under UVB and was accompanied by higher conditioned medium 25(OH)D3 and a lower sterol-pool readout. DHCR7 knockdown produced concordant shifts in these readouts, supporting a contributory role for DHCR7. Together, these findings support the presence of a UVB-responsive OPN1SW-DHCR7 module that may contribute to keratinocyte adaptation to UVB exposure.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}