Journal of dermatological science最新文献

{"title":"Classifying novel DSG1 variants on disease severity in SAM syndrome and palmoplantar keratoderma","authors":"Vanya S.V.J. Rossel ,&nbsp;Jaap J.A.J. van der Velden ,&nbsp;Renske Janssen ,&nbsp;Bert L. Callewaert ,&nbsp;Aude Beyens ,&nbsp;Fanny Morice-Picar ,&nbsp;Maaike Vreeburg ,&nbsp;Peter C. van den Akker ,&nbsp;Saskia M. Maas ,&nbsp;Gilles F.H. Diercks ,&nbsp;Antoni H. Gostyński ,&nbsp;Marieke C. Bolling ,&nbsp;Peter M. Steijlen ,&nbsp;Marike W. van Gisbergen ,&nbsp;Michel van Geel","doi":"10.1016/j.jdermsci.2026.01.007","DOIUrl":"10.1016/j.jdermsci.2026.01.007","url":null,"abstract":"<div><h3>Background</h3><div>Biallelic pathogenic variants in <em>DSG1</em> encoding desmoglein 1 cause severe atopic dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, whereas heterozygous variants result in palmoplantar keratoderma (PPK).</div></div><div><h3>Objectives</h3><div>Here we investigate genetic variants, pathophysiology and clinical findings of three patients with SAM syndrome and eleven patients diagnosed with PPK.</div></div><div><h3>Methods</h3><div>Genetic analysis was used to identify variants in <em>DSG1</em>. Immunofluorescence staining was performed to determine DSG1 protein expression in SAM patients.</div></div><div><h3>Results</h3><div>In SAM syndrome and PPK patients eleven novel variants in <em>DSG1</em> were identified. In the SAM patients with a severe, intermediate and mild phenotype, we identified compound heterozygous, a known dominant, and homozygous variants, respectively, while clinical variability in PPK patients was observed. The variants in <em>DSG1</em> for SAM and PPK included scarcely reported missense (n = 4), nonsense (n = 4), splice-site (n = 2) variants, a small deletion/duplication (n = 3) and a never reported gross deletion (n = 1). Immunofluorescence staining in skin of SAM patients showed that the severity of the symptoms correlates with total or partial extracellular absence of DSG1, suggesting a potential difference in protein stability. Hence, loss-of-function variants that occur in the extracellular or transmembrane domains of DSG1, resulted in loss of intercellular connecting and anchoring capability, while intracellular variants, partly preserve the adhesive function of DSG1.</div></div><div><h3>Conclusion</h3><div>Our results contribute to better understanding the genotype-phenotype correlation associated with <em>DSG1</em> variants, although the exact pathophysiological mechanisms remain to be elucidated.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 3","pages":"Pages 22-31"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358150","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}

{"title":"Councilors’ Meeting/General Assembly of Members at the 50th Annual General Meeting of the Japanese Society for Investigative Dermatology (JSID)","authors":"","doi":"10.1016/j.jdermsci.2026.03.001","DOIUrl":"10.1016/j.jdermsci.2026.03.001","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 3","pages":"Pages 36-39"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557065","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}

{"title":"Oxidative stress induced TSLP production via TRPV4 regulates type 2 inflammation and pruritus in MC903 induced atopic dermatitis mouse model","authors":"Keiji Kosaka ,&nbsp;Akihiko Uchiyama ,&nbsp;Yuta Inoue ,&nbsp;Mai Ishikawa ,&nbsp;Takeshi Araki ,&nbsp;Shintaro Saito ,&nbsp;Akiko Sekiguchi ,&nbsp;Yoko Yokoyama ,&nbsp;Sachiko Ogino ,&nbsp;Ryoko Torii ,&nbsp;Yuki Watanuki ,&nbsp;Koji Shibasaki ,&nbsp;Sei-ichiro Motegi","doi":"10.1016/j.jdermsci.2026.01.005","DOIUrl":"10.1016/j.jdermsci.2026.01.005","url":null,"abstract":"<div><h3>Background</h3><div>Transient receptor potential vanilloid 4 (TRPV4) is a calcium ion channel that is widely expressed in various cells, and it regulates multiple physiological and pathological processes. In skin, TRPV4 senses temperature, mechanical and chemical stimuli. Although TRPV4 has been shown to regulate inflammatory in psoriasis, its role in atopic dermatitis (AD) remains unclear.</div></div><div><h3>Objective</h3><div>We aimed to elucidate the role of TRPV4 is AD pathogenesis and its potential as therapeutic target.</div></div><div><h3>Methods</h3><div>We used human skin samples from healthy and patients with AD for immunostaining. TRPV4 knock out (KO) mice and MC903-induced AD mouse models were used in vivo. HaCaT cells were used in vitro.</div></div><div><h3>Results</h3><div>TRPV4 was highly expressed in keratinocytes in lesional skin site of AD. TRPV4 KO mice had less severe dermatitis, barrier dysfunction and pruritus than WT mice in MC903-treated mouse model. TRPV4 KO mice had significantly decreased mRNA expression of type 2 inflammatory cytokines, including TSLP, interleukin (IL)-4, IL-13, and IL-31 via qPCR, and reduced protein levels of TSLP and IL-4 by ELISA. In vitro, oxidative stress promoted expression and activation of TRPV4, following enhanced TSLP expression in HaCaT cells. However, stimulation with IL-4 and IL-13 inhibited TRPV4 activation in HaCaT cells. Finally, treatment with selective TRPV4 antagonist HC-067047 significantly reduced the severity of MC903-induced AD-like dermatitis.</div></div><div><h3>Conclusion</h3><div>Our findings showed that TRPV4 mediates the expression of keratinocyte-derived TSLP and increases Th2 immunity and pruritus, highlighting TRPV4 as a novel therapeutic strategy for the treatment of AD.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 3","pages":"Pages 1-11"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168641","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}

{"title":"Identification of novel small molecule compounds with readthrough activity in Nagashima-type palmoplantar keratosis.","authors":"Jin Teng Peh, Takato Sugiyama, Risa Nobuta, Toshinari Miyauchi, Shotaro Suzuki, Masae Takeda, Yuka Ohguchi, Hideyuki Ujiie, Toshifumi Nomura","doi":"10.1016/j.jdermsci.2026.02.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2026.02.001","url":null,"abstract":"<p><strong>Background: </strong>Nagashima-type palmoplantar keratosis (NPPK), the most common form of hereditary palmoplantar keratodermas in East Asian populations, is caused by biallelic loss-of-function mutations in SERPINB7 such as p.Arg266Ter (c.796 C>T). This mutation introduces a premature termination codon (PTC). Given the minimal efficacy of current drugs in improving NPPK skin phenotypes, we applied readthrough therapy to enable the production of functional proteins by allowing ribosomes to read through premature stop codons.</p><p><strong>Objective: </strong>To discover small molecule compounds with readthrough potency.</p><p><strong>Methods: </strong>Using high-throughput screening, we initially screened nearly 20,000 small molecule compounds. Using Western blot, we assessed the readthrough effectiveness of shortlisted compounds on the mutant SERPINB7 vector. We identified a promising compound and acquired structurally related compounds, comparing then their potency with that of gentamicin and ataluren. In addition, we evaluated the readthrough capability of the identified compounds on other 11 premature termination codons with different + 4 nucleotides.</p><p><strong>Results: </strong>The identified hit compounds demonstrated superior readthrough efficacy than gentamicin and ataluren. Notably, our compounds were effective in enabling readthrough, particularly on UGAA and UAAG premature stop codons.</p><p><strong>Conclusion: </strong>Our research identified new compounds that effectively promote the readthrough of premature stop codons. In vitro, these compounds showed higher readthrough potency than drugs such as gentamicin or ataluren. These results suggest that these compounds could be promising therapeutic agents for genetic diseases caused by nonsense mutations.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793169","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}

{"title":"Editors choice","authors":"","doi":"10.1016/S0923-1811(26)00029-0","DOIUrl":"10.1016/S0923-1811(26)00029-0","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 2","pages":"Page ii"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147408653","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}

{"title":"Integrative analysis of bulk multiomics and single-cell transcriptomics reveals the value of neddylation in Skin Cutaneous Melanoma","authors":"Li Yang ,&nbsp;Yuan Yao ,&nbsp;Kexin Shi ,&nbsp;Jun Tian ,&nbsp;Lei Zhang","doi":"10.1016/j.jdermsci.2025.12.003","DOIUrl":"10.1016/j.jdermsci.2025.12.003","url":null,"abstract":"<div><h3>Background</h3><div>Melanoma is recognized as the most aggressive type of skin cancer, characterized by its high mortality rates and significant therapeutic challenges.</div></div><div><h3>Objective</h3><div>The primary aim of this research is to analyze cellular heterogeneity in SKCM through single-cell RNA sequencing (scRNA-seq) and construct a neddylation-related prognostic model.</div></div><div><h3>Methods</h3><div>The scRNA-seq and bulk data of Skin Cutaneous Melanoma (SKCM) samples were obtained from Gene Expression Omnibus and Cancer Genome Atlas Program databases. The nonnegative matrix factorization clustering algorithm was employed to stratify malignant cells into different neddylation cell subtypes in SKCM.</div></div><div><h3>Results</h3><div>The scRNA-seq analysis classified 31,894 high-quality cells into eight major cell types, revealing significant cellular distribution patterns within the TME. We observed that neddylation activity was significantly elevated in SKCM tissues compared to normal counterparts. Based on the expression profile of prognostic NRGs, the malignant cells were stratified into four neddylation cell subtypes in SKCM. A neddylation-related prognostic signature (NRPS) was established based on marker genes of neddylation-C3 cell subtype. The low-risk group activated immune-related signaling pathways, while the high-risk group activated various cancer-related pathways. Notably, the low-risk group exhibited better overall survival, higher immune cell infiltration, and response rates to immunotherapy compared to the high-risk group.</div></div><div><h3>Conclusion</h3><div>This investigation emphasizes the crucial function of NRGs in the prognosis of SKCM, while also underscoring the importance of understanding the TME and its cellular heterogeneity. The distinct cellular composition and functional attributes within the TME highlight the potential for immunotherapy responses that can be stratified by risk.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 2","pages":"Pages 37-47"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013820","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}

{"title":"DcR3 reprograms macrophage plasticity to promote wound healing and hair regeneration","authors":"Shih-Hsun Ou ,&nbsp;Yi-Chun Chen ,&nbsp;Shie-Liang Hsieh ,&nbsp;Chih-Chiang Chen","doi":"10.1016/j.jdermsci.2026.01.002","DOIUrl":"10.1016/j.jdermsci.2026.01.002","url":null,"abstract":"<div><h3>Background</h3><div>Macrophages are key regulators of tissue repair, with M2-polarized subsets promoting anti-inflammatory, pro-regenerative functions. Decoy Receptor 3 (DcR3), a soluble TNF receptor superfamily member, modulates macrophage polarization, but its role in cutaneous regeneration remains unclear.</div></div><div><h3>Objective</h3><div>To elucidate the immunomodulatory role of DcR3 in macrophage polarization and evaluate its therapeutic potential in skin wound repair and hair follicle regeneration.</div></div><div><h3>Methods</h3><div>We employed a combination of in vitro macrophage polarization assays with in vivo models, including delayed wound healing and mechanical stretch-induced hair regeneration, to evaluate DcR3-mediated immunoregulation. Transgenic mice with macrophage-specific DcR3 overexpression were employed to investigate the physiological function of endogenous DcR3.</div></div><div><h3>Results</h3><div>DcR3 accelerated wound closure and dampened pro-inflammatory gene expression in LPS-treated wounds. While physiological hair cycling remained unchanged in DcR3-transgenic mice, mechanical stimulation elicited enhanced anagen induction. In vitro, DcR3 attenuated M1 polarization while amplifying IL-4-induced M2 gene expression, thereby promoting macrophage plasticity. Adoptive transfer of DcR3-reprogrammed macrophages improved both wound healing and hair regrowth by reshaping the wound microenvironment, reducing iNOS2⁺ M1-like and increasing CD206⁺ M2-like macrophage, while enriching the transitional iNOS2⁺CD206⁺ macrophage population.</div></div><div><h3>Conclusion</h3><div>DcR3 facilitates macrophage reprogramming toward reparative phenotypes and enhances regenerative responses in skin and hair follicles, establishing DcR3 as a promising immunoregulatory target for chronic wound management and alopecia treatment.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 2","pages":"Pages 27-36"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021249","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}

{"title":"Comparative analysis of cytotoxic mediators in Stevens–Johnson syndrome and toxic epidermal necrolysis using ex vivo human epidermis","authors":"Manao Kinoshita ,&nbsp;Youichi Ogawa ,&nbsp;Yuka Nagasaka ,&nbsp;Andrew Gibson ,&nbsp;Ramesh Ram ,&nbsp;Shinji Shimada ,&nbsp;Akira Momosawa ,&nbsp;Elizabeth J. Phillips ,&nbsp;Riichiro Abe ,&nbsp;Tatsuyoshi Kawamura","doi":"10.1016/j.jdermsci.2025.12.002","DOIUrl":"10.1016/j.jdermsci.2025.12.002","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 2","pages":"Pages 66-69"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968210","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}

{"title":"Salvianolic acid B ameliorate alopecia by simultaneously targeting Wnt/β-catenin and mTORC2/Akt signaling","authors":"Junjie Cen ,&nbsp;Xin Tang ,&nbsp;Nan Xu ,&nbsp;Yiyong Hong ,&nbsp;Tian Liu ,&nbsp;Lei Zhou ,&nbsp;Zhikai Liao ,&nbsp;Miaojian Wan","doi":"10.1016/j.jdermsci.2026.01.001","DOIUrl":"10.1016/j.jdermsci.2026.01.001","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia is a prevalent clinical condition with currently limited therapeutic options. Salvianolic acid B (Sal B) has demonstrated promising regenerative properties across various disease models. However, its potential role in the treatment of alopecia and the underlying mechanisms remain largely unexplored.</div></div><div><h3>Objective</h3><div>To elucidate the role and mechanisms of Sal B in hair regeneration, we evaluated its effects on hair loss model in vivo and in vitro, and integrated multi-omics analysis.</div></div><div><h3>Methods</h3><div>We performed reverse molecular docking screening using the LRP6 receptor (PDB: 7NAM) to identify Sal B as a top candidate. Network pharmacology and molecular docking were used to predict target genes and binding affinity. Sal B was treated with cultured DPCs and hair follicles to investigate its effects on DPC proliferation. In vivo efficacy was evaluated in murine alopecia and AGA. Integrated multi-omics analysis, complemented by Western blot and PCR, was employed to elucidate the key signaling pathways.</div></div><div><h3>Results</h3><div>Sal B bound strongly to LRP6 and promoted DPC proliferation, migration, and stemness. It enhanced hair shaft elongation in vitro and stimulated hair regeneration in mice, outperforming minoxidil in AGA models. Multi-omics analyses revealed enrichment in mTOR signaling, matrix metalloproteinases (MMPs), and MAPK pathways. Sal B activated mTORC2/Akt signaling, upregulated RICTOR, downregulated DEPTOR, and enhanced phosphorylation of Akt and GSK-3β, leading to β-catenin stabilization. It also increased expression of MMP9, MMP3, MMP1, and activated ERK and p38.</div></div><div><h3>Conclusion</h3><div>Sal B promotes hair regeneration through dual activation of the Wnt/β-catenin and mTORC2/Akt pathways, and upregulation of MMPs and MAPKs.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 2","pages":"Pages 56-65"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020347","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}

{"title":"A possible link between epidermal TRPV4 expression, osmolality, and itch in atopic dermatitis.","authors":"Atsuko Kamo, Mao Hotta, Mitsutoshi Tominaga, Kenji Takamori","doi":"10.1016/j.jdermsci.2026.01.008","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2026.01.008","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793172","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}