Journal of dermatological science最新文献

{"title":"Regulation of melanogenesis via ubiquitin-proteasome system and autophagy by 3,3,5-trimethylcyclohexyl succinate dimethylamide and tranexamic acid.","authors":"Jing Wang, Fanglan Zha, Simin Lin, Yun Wei, Lingling Xuan, Zhangying Ye, Hu Huang","doi":"10.1016/j.jdermsci.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.09.004","url":null,"abstract":"<p><strong>Background: </strong>Excessive melanogenesis in skin melanocytes results in hyperpigmentation disorders.</p><p><strong>Objective: </strong>This study investigates the combined effects and mechanisms of 3,3,5-trimethylcyclohexanol succinate dimethylamide (335, a succinic acid derivative) and tranexamic acid (TXA) on melanogenesis.</p><p><strong>Methods: </strong>Skin penetration of 335 was assessed via Raman spectroscopy. Interactions between 335 and TXA were predicted by molecular docking. The anti-melanogenic effect was evaluated by measuring melanin content in human keratinocytes (HaCaT) and mouse melanoma cells (B16). Transcriptome sequencing was performed to identify key pathways by which 335 regulates melanogenesis. Melanosomes were isolated from human melanoma cells (MNT-1) and co-cultured with keratinocytes to validate the specific mechanisms. A 3D melanin skin model was established to evaluate the anti-pigmentation effect of 335 and TXA by analyzing apparent chroma, lightness (L*), and melanin content and distribution.</p><p><strong>Results: </strong>The skin penetration of 335 was enhanced by the addition of TXA, and the two compounds exhibited hydrogen bonding and hydrophobic interactions. The combination of 335 and TXA (1:10) significantly reduced the melanin content in B16 cells compared to individual treatments. Transcriptomics revealed 335 modulates the ubiquitin-proteasome system (UPS) and autophagy. Experimental validation confirmed that 335 and TXA combination inhibited melanin production by promoting ubiquitination degradation of tyrosinase and autophagic degradation of melanosomes. In the 3D skin model, the combination enhanced skin brightness (apparent chroma and L* value) and reduced melanin deposition.</p><p><strong>Conclusion: </strong>The combination of 335 and TXA inhibits melanogenesis by UPS-mediated tyrosinase degradation and autophagy-driven melanosome degradation, offering a promising strategy for hyperpigmentation treatment.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228639","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":"Foxp3-ablation/melanoma-induced vitiligo: An enhanced mouse model.","authors":"Shiyu Jin, Sheng Wan, Xiuzu Song, Cuiping Guan","doi":"10.1016/j.jdermsci.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.09.002","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228691","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":"Deep intronic variant in TYR causes OCA1A in Japanese families through pseudoexon activation.","authors":"Ken Okamura, Toru Saito, Sachiko Ohori, Fumio Takada, Toshifumi Nomura, Etsuko Oba, Yutaka Hozumi, Tamio Suzuki","doi":"10.1016/j.jdermsci.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.09.003","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214844","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":"NELL2-Robo3 signaling promotes keratinocyte proliferation and inhibits keratinocyte apoptosis in condyloma acuminatum through autocrine and paracrine mechanisms.","authors":"Xiaohang Xie, Charat Rin, Yinyi Feng, Yichuan Li, Deqiao Qin, Yuchun Cao, Xiaochao Zhang, Yong Zhang","doi":"10.1016/j.jdermsci.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.09.001","url":null,"abstract":"<p><strong>Background: </strong>Condyloma acuminatum (CA) is caused by low-risk HPV infection and characterized by benign epithelial proliferation. NELL2, as a secreted glycoprotein, is strongly linked to dermatosis, but its function in CA remains unknown.</p><p><strong>Objective: </strong>To investigate the expression, function and mechanism of NELL2 in CA.</p><p><strong>Methods: </strong>The expression of NELL2 was detected in CA and normal skin tissues. HaCaT cells stably expressing HPV11-E7 (HPV11-E7-HaCaT) and control group (Vector-HaCaT) were constructed to explore the relationship between HPV infection and NELL2 expression. We downregulated NELL2 expression in HPV11-E7-HaCaT cells and added recombinant human NELL2 to medium of Vector-HaCaT and HPV11-E7-HaCaT cells to examine the effects of NELL2 on cell proliferation and apoptosis. The activation of MAPK pathway and the role of Robo3 were evaluated to explore the mechanisms underlying these effects.</p><p><strong>Results: </strong>NELL2 was overexpressed in CA, and increased NELL2 expression was positively associated with high HPV copy number and high Ki67 expression. HPV11-E7 induced the expression of NELL2 in HaCaT cells. In addition, NELL2 promoted proliferation and inhibited apoptosis in HPV11-E7-HaCaT and Vector-HaCaT cells through autocrine and paracrine mechanisms. NELL2 treatment activated the ERK pathway, and ERK inhibition by U0126 confirmed that ERK pathway was essential for the function of NELL2 in CA. Moreover, Robo3 acts as the NELL2 receptor in CA.</p><p><strong>Conclusion: </strong>NELL2 binds Robo3 to promote keratinocyte proliferation and inhibit keratinocyte apoptosis in CA through autocrine and paracrine mechanisms. NELL2-Robo3 signaling may be regarded as a potential target for CA treatment in the future.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152463","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":"Dermal fibroblast subsets and their roles in inflammatory and autoimmune skin diseases.","authors":"Takehiro Takahashi","doi":"10.1016/j.jdermsci.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.08.004","url":null,"abstract":"<p><p>Fibroblasts are mesenchymal cells that constitute the stroma across tissues. Historically, they have long been perceived as uniform structural cells passively residing in the background during the immune responses within tissues. However, a growing number of recent studies have revealed that fibroblasts are highly heterogeneous and dynamic, responding to various external stimuli with notable plasticity. They exhibit heterogeneity not only across tissues but also within the same organ, and show dynamic changes over time throughout development and aging. As a barrier tissue, the skin is constantly exposed to numerous environmental stressors and pathogens and is capable of mounting diverse yet robust immune responses to these stimuli. Reflecting this inherent nature, skin dermal fibroblasts are remarkably heterogeneous and dynamic. Upon tissue inflammation, they produce and secrete not only inflammatory cytokines and chemokines but also extracellular matrix molecules that critically modulate immune cell infiltration. They also engage in direct mechano-chemical interactions with neighboring cells and actively support neural growth. Furthermore, they function as antigen presenting cells and contribute to the formation of tertiary lymphoid structures. This review highlights recent advances in understanding the heterogeneity of dermal fibroblast subpopulations and their roles in the pathogenesis of major inflammatory and autoimmune skin diseases.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214798","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":"Eupatilin attenuates vemurafenib resistance through inhibition of ABCB1 in melanoma","authors":"Daishi Li ,&nbsp;Sitao Liu ,&nbsp;Yi Ge ,&nbsp;Hui Li ,&nbsp;Xinchen Ke ,&nbsp;Dongsheng Cao ,&nbsp;Guangtong Deng ,&nbsp;Lixia Lu ,&nbsp;Juan Su","doi":"10.1016/j.jdermsci.2025.06.003","DOIUrl":"10.1016/j.jdermsci.2025.06.003","url":null,"abstract":"<div><h3>Background</h3><div>The clinical efficacy of vemurafenib<span> in melanoma patients has been hindered by the development of acquired resistance.</span></div></div><div><h3>Objectives</h3><div>To comprehend the molecular signaling pathways underlying this resistance and identify potential strategies to overcome it.</div></div><div><h3>Methods</h3><div><span>We first constructed the vemurafenib-resistant melanoma cell lines A375R and identified ABCB1 as a potential driver through </span>RNA sequence<span>. ABCB1 knockdown on vemurafenib<span> sensitivity was assessed by CCK-8 and colony formation. FDA-approved eupatilin was identified as a novel ABCB1 inhibitor by employing the quantitative structure-activity relationship model and ADMETlab 2.0. The combined effect of eupatilin and vemurafenib was detected in in vitro and in vivo.</span></span></div></div><div><h3>Results</h3><div>The expression of ABCB1 was upregulated in A375R. The genetic inhibition of ABCB1 could restore sensitivity to vemurafenib in resistant cells. Eupatilin was a previously unexplored compound that can selectively target ABCB1 and exhibit favorable safety profiles. Notably, we identified eupatilin as a therapeutic intervention to counteract acquired resistance to vemurafenib in cell and animal experiments, resulting in the inhibition of tumor growth. Furthermore, we found upregulation of ABCB1 in resistant cells due to the activation of the PI3K-AKT-mTOR pathway.</div></div><div><h3>Conclusion</h3><div>These findings provided valuable insights into a novel molecular mechanism underlying vemurafenib resistance and highlighted potential ABCB1 as a viable target, in conjunction with its novel inhibitor eupatilin, to enhance effectiveness of vemurafenib.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 3","pages":"Pages 112-121"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593248","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":"Difamilast induces human beta defensin 3 production via CREB and NRF2 in human keratinocytes","authors":"Gaku Tsuji ,&nbsp;Ayako Yumine ,&nbsp;Masaki Takemura ,&nbsp;Takeshi Nakahara","doi":"10.1016/j.jdermsci.2025.07.003","DOIUrl":"10.1016/j.jdermsci.2025.07.003","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 3","pages":"Pages 135-138"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812757","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 genomic and transcriptomic profiling reveals dysregulation of FOXA1-AGR2 axis in penoscrotal extramammary Paget's disease","authors":"Daoning Zhang ,&nbsp;Sini Gao ,&nbsp;Chunxia Zhao ,&nbsp;Xiaomin Cai ,&nbsp;Ruiqin Mai ,&nbsp;Guohong Zhang ,&nbsp;Hang Li","doi":"10.1016/j.jdermsci.2025.06.002","DOIUrl":"10.1016/j.jdermsci.2025.06.002","url":null,"abstract":"<div><h3>Background</h3><div>Extramammary Paget's disease (EMPD) is a rare cutaneous mucinous adenocarcinoma primarily affect the penoscrotal skin, characterized by the presence of Paget cells scattered within the epidermis. The molecular features of Paget cells remain poorly understood.</div></div><div><h3>Objectives</h3><div>To describe the genomic and transcriptomic landscape of penoscrotal EMPD, identify the driver mutation or core transcription factor through integrative analysis, identify biological markers and provide new insights for the pathogenesis of penoscrotal EMPD.</div></div><div><h3>Methods</h3><div>Whole exome sequencing was performed on penoscrotal EMPD tissues from 37 patients, of whom 28 patients also underwent RNA sequencing, and the findings was validated in an additional 72 patients, encompassing 120 multi-region tumor tissues to identify core transcription factors. The dysregulation was further confirmed by immunohistochemistry.</div></div><div><h3>Results</h3><div>Genomic landscape did not reveal <em>FOXA1</em> or <em>SPDEF</em> mutations penoscrotal EMPD. Transcriptomic profiling identified the upregulation of lineage-specific transcription factors <em>FOXA1</em> and <em>SPDEF,</em> along with their targeted genes <em>AGR2</em> and <em>MUC5AC</em>. Upregulation of <em>FOXA1</em>, <em>SPDEF</em> and <em>AGR2</em> without gene fusion were consistently replicated in the validation cohort. Further analysis of multiple tissue regions confirmed <em>FOXA1</em> and <em>SPDEF</em> as driver transcription factors in penoscrotal EMPD. We identify key transcription factors regulating co-expressed modules <em>FOXA1-SPDEF-AGR2</em>, suggesting goblet cells features of penoscrotal EMPD. The immunohistochemistry confirmed the co-expression of FOXA1-AGR2 pattern in Paget cells.</div></div><div><h3>Conclusions</h3><div>Our study provides novel insights into the molecular characteristics of Paget cells, and also highlights the critical role of FOXA1 in Paget cell development in EMPD.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 3","pages":"Pages 122-131"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700776","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":"Preferential CD101 expression on resident memory regulatory T cells and IFN-γ-producing CD8+ resident memory T cells in human epidermis","authors":"Takuya Sato ,&nbsp;Youichi Ogawa ,&nbsp;Manao Kinoshita ,&nbsp;Yuka Nagasaka ,&nbsp;Shinji Shimada ,&nbsp;Akira Momosawa ,&nbsp;Tatsuyoshi Kawamura","doi":"10.1016/j.jdermsci.2025.07.002","DOIUrl":"10.1016/j.jdermsci.2025.07.002","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 3","pages":"Pages 132-134"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818867","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":"17β-Estradiol promotes LL37-induced rosacea-like skin inflammation via G protein-coupled estrogen receptor 30","authors":"Jin Tang ,&nbsp;Peng Chen ,&nbsp;Chuchu Huang ,&nbsp;Wanjing Wang ,&nbsp;Ben Wang ,&nbsp;Wei Shi ,&nbsp;Yan Tang ,&nbsp;Zhili Deng ,&nbsp;Yiya Zhang ,&nbsp;Ji Li ,&nbsp;Dan Jian","doi":"10.1016/j.jdermsci.2025.05.005","DOIUrl":"10.1016/j.jdermsci.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Rosacea is a common chronic inflammatory skin condition that predominantly affects females, though its underlying mechanisms remain unclear.</div></div><div><h3>Objective</h3><div>To explore the role of 17β-estradiol (E2) and the G-coupled estrogen receptor 30 (GPR30) in the pathogenesis of rosacea.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional analysis of UK Biobank data to investigate the association between exogenous hormone use and rosacea risk in females. Additionally, ovariectomized (OVX) LL37-induced rosacea mouse models were utilized to evaluate the effects of ovarian E2 loss and exogenous E2 supplementation. GPR30 expression was measured in rosacea skin lesions, LL37-treated mice, and HaCaT keratinocytes. The impact of GPR30 deletion on rosacea inflammation was assessed using GPR30 knockout mice. Finally, the efficacy of GPR30 inhibition or silencing in reducing inflammation was examined in LL37 or LL37 plus E2 treated mice and HaCaT cells.</div></div><div><h3>Results</h3><div>UK Biobank data revealed significant associations between oral contraceptive use (OR: 1.20; 95 % CI: 1.06, 1.37) and hormone-replacement therapy (OR: 1.31; 95 % CI: 1.18, 1.46) with increased rosacea risk. OVX mice exhibited reduced skin erythema and dermal infiltration, effects reversed by E2 supplementation, which exacerbated rosacea inflammation. GPR30 was overexpressed in rosacea lesions, LL37-treated mice, and HaCaT cells, with TFAP2C potentially mediating this effect. GPR30-deficient mice showed reduced inflammation, while GPR30 inhibition or knockdown significantly improved rosacea-like inflammation in LL37 or LL37 plus E2 treated models.</div></div><div><h3>Conclusion</h3><div>Activation of the E2/GPR30 pathway plays a significant role in rosacea inflammation, and GPR30 inhibition may represent a novel therapeutic strategy for rosacea.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 3","pages":"Pages 101-111"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651667","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}