Experimental Dermatology最新文献

{"title":"Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation","authors":"Rui Mao,&nbsp;Fan Wang,&nbsp;Tongtong Zhang,&nbsp;Ji Li","doi":"10.1111/exd.70161","DOIUrl":"https://doi.org/10.1111/exd.70161","url":null,"abstract":"<div>\u0000 \u0000 <p>The current therapeutic landscape for rosacea is notably deficient in targeted medications, underscoring an urgent need for the identification of novel biomarkers. Utilising a longitudinal cohort of 54 306 individuals from the UK Biobank (UKB), we conducted a comprehensive assessment of the associations between 2923 serum proteins and the risk for rosacea. Our cohort analysis identified 18 proteins significantly associated with rosacea risk. Next, we complemented the two-sample Mendelian randomisation (TSMR) and Mendelian randomisation (SMR) analysis based on pooled data to identify genetic links between protein targets and rosacea. TSMR analysis refined this list to nine proteins demonstrating significant causal relationships with at least one form of rosacea. Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it. The differential expression of these five biomarkers was validated by multiple omics datasets as well as in vitro experiments. We calculated the protein score based on the expression levels of these proteins, noting that participants with higher scores demonstrated an increased incidence of rosacea. The integrative examination of proteomic and genetic data from a European adult cohort provides robust causal evidence for several proteins as promising new biomarkers for the development of rosacea treatments.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927356","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":"Genetic Comorbidity of Psoriasis and Four Cardiovascular Diseases: Uncovering Shared Mechanisms and Potential Therapeutic Targets","authors":"Xiaojian Li,&nbsp;Zhangren Yan,&nbsp;Hongrong Lan,&nbsp;Yanyu Wu,&nbsp;Shiyu Chen,&nbsp;Guirong Qiu,&nbsp;Yunbo Wu","doi":"10.1111/exd.70158","DOIUrl":"https://doi.org/10.1111/exd.70158","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis (PSO) is a chronic, systemic immune-mediated inflammatory disease that has been increasingly recognised as being significantly comorbid with various cardiovascular diseases (CVDs). However, the underlying shared genetic architecture and biological mechanisms connecting these conditions remain largely unclear. This study aimed to systematically evaluate the genetic correlations between PSO and four major CVDs—hypertension, coronary heart disease, coronary atherosclerosis, and heart failure—and to identify shared genetic loci, functional genes, and immune-mediated pathways that may serve as potential targets for comorbidity intervention. We integrated multiple large-scale publicly available genome-wide association study datasets and employed a multidimensional genetic analysis framework. This included linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), stratified LDSC (S-LDSC), multi-dimensional gene-set enrichment (MAGMA), pleiotropy analysis under the composite null hypothesis (PLACO), and summary-data-based Mendelian randomisation (SMR). These approaches were used to elucidate the shared genetic architecture and to functionally annotate the biological mechanisms underlying PSO–CVD comorbidity. LDSC and HDL analyses revealed significant positive genetic correlations between PSO and all four CVDs (<i>p</i> &lt; 0.05). PLACO identified a total of 653 pleiotropic SNPs, enriched in key genomic loci such as 12q24.12 (e.g., SH2B3, BRAP) and 5q31.1 (e.g., IL3, C5orf56). S-LDSC results demonstrated significant enrichment of these shared signals in disease-relevant tissues including the aorta, coronary arteries, peripheral blood, and spleen. Immune colocalization analysis further highlighted the involvement of T cells, monocytes/macrophages, and NK cells in the genetic comorbidity between PSO and CVDs. Integrative analyses combining MAGMA, SMR, and FUMA identified multiple potential therapeutic targets, such as APOE, IL13, and C5orf56, that may play key roles in the pathogenesis of both diseases. This study provides the first comprehensive genetic dissection of the comorbidity between PSO and CVDs. We propose a “genetics–immunity–tissue” regulatory model underlying the shared pathophysiology. Our findings provide potential evidence that PSO, as a systemic condition, may influence cardiovascular pathophysiology.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905270","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":"Trained Immunity and Its Potential Implications in the Etiopathogenesis of Hidradenitis Suppurativa: A New Paradigm in Chronic Inflammation?","authors":"Annalisa Marcuzzi,&nbsp;Erika Rimondi,&nbsp;Giada Lodi,&nbsp;Marta Manfredini,&nbsp;Paola Maura Tricarico,&nbsp;Chiara Moltrasio,&nbsp;Angelo Valerio Marzano,&nbsp;Muhammad Suleman,&nbsp;Paola Secchiero,&nbsp;Elisabetta Melloni,&nbsp;Sergio Crovella","doi":"10.1111/exd.70160","DOIUrl":"https://doi.org/10.1111/exd.70160","url":null,"abstract":"<p>Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin disorder characterised by recurrent, painful nodules, abscesses and tunnels, often leading to tissue destruction with a significant impairment in quality of life. Despite advancements in understanding, HS remains a complex disease, whose exact pathogenesis is yet to be revealed. Nevertheless, the role of a dysregulated innate immune response has been established, potentially contributing to the persistent and chronic inflammation. Recent advances in immunology have highlighted the concept of trained immunity, a form of innate immune memory that may provide new insights into HS pathophysiology. Trained immunity is mediated by epigenetic and metabolic reprogramming of innate immune cells, enabling them to mount a heightened and prolonged inflammatory response upon subsequent stimuli, even in the absence of the original trigger. We hypothesize that trained immunity could contribute to the persistent inflammatory state, influencing HS progression and severity. Environmental and microbial factors may act as persistent stimuli, leading to activation of innate immune pathways. From a mechanistic perspective, trained immunity in HS might involve increased cytokine production, altered myeloid cell differentiation and persistent epigenetic modifications favouring a pro-inflammatory phenotype. Identifying specific molecular markers associated with trained immunity in HS could provide new diagnostic and prognostic tools and may open novel therapeutic avenues. By exploring the potential role of trained immunity in HS, we provide a new perspective on chronic inflammation, thus hypothesizing another actor involved in the aetiology/pathogenesis of this complex disease.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905441","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":"Clinical, Dermoscopic and Reflectance Confocal Microscopy Characteristics Associated With the Presence of Negative Pigment Network Among Spitzoid Neoplasms","authors":"Marco Spadafora,&nbsp;Francesca Farnetani,&nbsp;Stefania Borsari,&nbsp;Shaniko Kaleci,&nbsp;Dafi Porat,&nbsp;Silvana Ciardo,&nbsp;Ignazio Stanganelli,&nbsp;Caterina Longo,&nbsp;Giovanni Pellacani,&nbsp;Alon Scope","doi":"10.1111/exd.70154","DOIUrl":"https://doi.org/10.1111/exd.70154","url":null,"abstract":"<p>Negative pigment network (NPN) is a dermoscopic structure frequently associated with melanoma. Though commonly observed in Spitz naevi (SN) and Spitzoid melanoma (SM), its reflectance confocal microscopy (RCM) correlates have been primarily studied in non-Spitzoid melanocytic neoplasms. This study aimed to identify clinical, dermoscopic, and RCM features associated with dermoscopic NPN in Spitzoid neoplasms and explore its histopathological correlates. We retrospectively analysed clinical, dermoscopic, and RCM images from 128 histopathologically confirmed SN and SM cases diagnosed between 2014 and 2020. Lesions were grouped by presence or absence of dermoscopic NPN, and comparisons were made across clinical, dermoscopic, and RCM features. A subset of 20 cases underwent histopathologic correlation. Of the 128 cases, 96 (74%) were SN and 32 (26%) SM. NPN was present in 58 lesions (45%)—40 SN (42%) and 18 SM (56%). NPN was associated with lesion diameter ≥ 5 mm, presence of shiny white structures, dotted vessels, and inversely associated with diffuse blue-white veil. SMs showed higher frequencies of asymmetry, multicomponent patterns, and extensive NPN. RCM features previously linked to NPN—round or linear surface disruptions, bright suprabasal areas, and broadened interpapillary spaces—were seen in 87% of cases but did not correlate with diagnosis or dermoscopic NPN. Corresponding histologic features included keratin-filled dells, hypergranulosis, and broadened rete ridges or infundibula. RCM correlates of dermoscopic NPN are frequently observed in Spitzoid neoplasms, independent of visible dermoscopic NPN, suggesting perceptibility may depend on contrast within dermoscopic patterns.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905268","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":"CCN1: A Dermo-Epidermal Crosstalk Mediator and Regulatory Protein in Cutaneous Homeostasis","authors":"Yanan Wu,&nbsp;Yingying Lin,&nbsp;Li Li,&nbsp;Miaomiao Guo,&nbsp;Yue Wu,&nbsp;Fan Yi","doi":"10.1111/exd.70157","DOIUrl":"https://doi.org/10.1111/exd.70157","url":null,"abstract":"<p>Cellular communication network factor 1 (CCN1), also known as cysteine-rich angiogenic inducer 61 (CYR61), is a pivotal member of the CCN family, which comprises six secretory matricellular proteins. CCN1 exhibits multifaceted biological functions, including regulation of cell proliferation, differentiation, senescence, angiogenesis and tissue repair. Current evidence demonstrates that CCN1 activates intracellular signalling cascades by binding to receptors such as integrins and heparan sulphate proteoglycans (HSPGs), thereby mediating its biological effects. Furthermore, CCN1 plays critical roles in diverse pathological conditions, including cutaneous wound healing, skin ageing, psoriasis, diabetic ulcers and melanoma. This review delineates the interaction between CCN1 and the extracellular matrix (ECM), highlighting its capacity to mediate dermo-epidermal communication and maintain skin structural homeostasis. As a tunable molecular target, CCN1 holds significant potential for addressing cutaneous disorders and enhancing skin health. Despite extensive investigations into its roles in dermatological diseases (e.g., psoriasis, melanoma), applications in cosmetics and cosmeceuticals remain nascent. Consequently, this study aims to elucidate the mechanistic contributions of CCN1 to skin physiology and pathology, providing a strategic framework for its translational exploitation in dermatological therapeutics and cosmeceutical innovation.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894196","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":"Complications of Mohs Surgery and the Influence of Economic Status on Outcomes","authors":"Christopher A. Guirguis,&nbsp;Lauren M. Ching,&nbsp;Melissa A. Pugliano-Mauro","doi":"10.1111/exd.70156","DOIUrl":"https://doi.org/10.1111/exd.70156","url":null,"abstract":"&lt;p&gt;Mohs micrographic surgery (MMS) remains an important part of care for cutaneous cancers. Nevertheless, disparities in access to MMS based on socio-economic status (SES) and geographic location persist. This study examines the relationship between income and complications following MMS. Prior literature has highlighted challenges in the accessibility of Mohs surgeons, with barriers to access in rural and lower-income areas [&lt;span&gt;1, 2&lt;/span&gt;]. This discrepancy may influence the complication rates and patient outcomes. Literature is sparse regarding the impacts of SES on MMS outcomes.&lt;/p&gt;&lt;p&gt;Our study queried the All of Us database (AoUDB) from the National Institute of Health for patients with a prior procedural history of MMS. We then queried for complications occurring within 30 and 60 days postoperatively. Survey data was used to group individuals based on annual income brackets. Complications among cohorts were compared using the Chi-square test of independence and the Bonferroni correction for pairwise analyses.&lt;/p&gt;&lt;p&gt;The database queries identified 7999 cases of MMS across 3668 patients. Among those cases, the rate of any of the queried complications occurring in the 30- and 60-day timeframes was 6.04% and 10.65%, respectively. Overall complication rates were inversely related to income bracket, aside from an increase in the highest bracket (&lt;i&gt;p&lt;/i&gt; = 0.005 and &lt;i&gt;p&lt;/i&gt; = 0.0003 for 30- and 60-day rates, respectively). At 30 days post-op, patients in the &lt; $10,000 annual income bracket (the lowest recorded income bracket) had a rate of 11.02%, while those in the 150,000–200,000annual income bracket (the second highest recorded income bracket) had a rate of 4.58%. At 60 days post-op, patients in the &lt; $10,000 annual income bracket had a rate of 15.25%, while those in the 150,000–200,000annual income bracket had a rate of 8.10%. Patients in the &gt; $200,000 annual income bracket (the highest recorded income bracket) had rates of 8.03% and 13.38% at 30 and 60 days, respectively.&lt;/p&gt;&lt;p&gt;Infections accounted for most complications (occurring in 3.99% of cases and 6.96% of cases at 30 and 60 days, respectively), with significant differences among cohorts (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). At 30 days, the &lt; $10 000 annual income bracket had a rate of 9.32%, the $150000–200 000 annual income bracket had a rate of 2.35% and the &gt; $200 000 annual income bracket had a rate of 4.46%. At 60 days, the infection rates were 11.86% for the &lt; $10 000 annual income bracket, 4.21% for the $150000–200 000 annual income bracket and 7.04% for the &gt; $200 000 annual income bracket.&lt;/p&gt;&lt;p&gt;Regarding all other complications, hypertrophic scarring and pigmentation changes displayed a bimodal distribution at the higher and lower brackets. There were significantly lower rates of dehiscence in the lowest brackets (Figure 1).&lt;/p&gt;&lt;p&gt;Upon adjusting for gender, sex, race and ethnicity using multiple linear regression, risk of infection and overall complication continu","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891700","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":"Calcipotriol Induces Thymic Stromal Lymphopoietin in Human Squamous Carcinoma Cells","authors":"Truelian Lee,&nbsp;Rosanna Monetta,&nbsp;Stefano Sol,&nbsp;Fabiana Boncimino,&nbsp;Sandro Goruppi,&nbsp;Tomonori Oka,&nbsp;Shadmehr Demehri","doi":"10.1111/exd.70155","DOIUrl":"https://doi.org/10.1111/exd.70155","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881183","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":"Advances in the Study of Pyroptosis in Dermatological Disorders","authors":"Shenghao Xue,&nbsp;Yumeng Lin,&nbsp;Lusheng Liu,&nbsp;Ke Wang,&nbsp;Qian Guo,&nbsp;Ruyi Zhang,&nbsp;Kaisheng Zeng,&nbsp;Jin Jiang,&nbsp;Zhinan Deng,&nbsp;Lan Yuan,&nbsp;Zhongyu Han,&nbsp;Xiaohong Zuo","doi":"10.1111/exd.70148","DOIUrl":"https://doi.org/10.1111/exd.70148","url":null,"abstract":"<p>Pyroptosis is a proinflammatory procedural cell die-off characterised by the forming of membrane pores that are mediated by a series of aerogelin proteins. Pyroptosis occurs by caspase-1 dependent typical signalling pathways, caspase-4/5/11 dependent atypical signalling pathways, and other signalling pathways (GSDME, GSDMD, GSDMA, GSDMB and GSDMC mediated signalling pathways). Pyroptosis may assist in the elimination of the pathogen as a type of mechanism of host defence, but pyroptosis-induced inflammation can lead to dysfunction and organ damage, exacerbating the pathology of the disease. Several existing researches have suggested that pyroptosis is implicated in the etiopathogenesis of a majority of dermatologic disorders, including systemic lupus erythematosus (SLE), psoriasis (PA), atopic dermatitis (AD), systemic sclerosis (SSc), vitiligo and chronic spontaneous urticaria (CSU). In this review, we examine the available literature, focusing on the mechanistic aspects of pyroptosis and the involvement of pyroptosis in the six dermatologic disorders mentioned above, to aid in further research in the future.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869569","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":"Platelet-Derived Extracellular Vesicles Alleviate Psoriatic Inflammation via Mitochondrial Transfer to Macrophages","authors":"Bing Wang,&nbsp;Dandan Li,&nbsp;Chaolan Pan,&nbsp;Yumeng Wang,&nbsp;Yidong Tan,&nbsp;Yijun Yang,&nbsp;Haifei Liu,&nbsp;Zhirong Yao,&nbsp;Hui Zhang,&nbsp;Zhicheng Wang","doi":"10.1111/exd.70152","DOIUrl":"https://doi.org/10.1111/exd.70152","url":null,"abstract":"<div>\u0000 \u0000 <p>Platelet-rich plasma (PRP) is a safe, autologous plasma component abundant in cytokines and extracellular vesicles, frequently applied to treat inflammatory disorders. Although PRP demonstrates potential for psoriasis therapy, its underlying mechanism remains insufficiently understood. In this study, various PRP constituents were evaluated in an imiquimod (IMQ)-induced mouse model of psoriasis. PRP, platelet-derived extracellular vesicles (PEVs), and platelet-poor plasma (PPP) were isolated from mice and administered subcutaneously. The data showed that PEVs, rather than PPP, served as the principal anti-psoriatic factor. Furthermore, RNA sequencing and flow cytometry revealed that PEVs markedly suppressed M1 polarisation of macrophages, thereby mitigating psoriatic-like inflammation. In vitro, PEVs delivered encapsulated mitochondria to RAW264.7 cells in a concentration-dependent manner. These functional organelles enhanced oxidative phosphorylation and suppressed glycolysis, driving a metabolic shift favouring an anti-inflammatory phenotype and attenuating the inflammatory response. In conclusion, PEVs emerge as the primary PRP component responsible for inflammatory suppression in psoriasis. Notably, mitochondria transfer mediated by PEVs underscores a promising therapeutic avenue and provides novel insight into the role of platelet derivatives in inflammatory diseases.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858607","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":"Suppression of Sebum Production by Vemurafenib Through Paradoxical ERK Activation Resulted in the Inhibition of the mTOR Pathway in 5α-Dihydrotestosterone-Differentiated Hamster Sebocytes In Vitro","authors":"Toshikazu Koiwai,&nbsp;Takashi Sato","doi":"10.1111/exd.70150","DOIUrl":"https://doi.org/10.1111/exd.70150","url":null,"abstract":"<p>Vemurafenib, a low-molecular-weight BRAF inhibitor, effectively treats cutaneous melanoma with the BRAF^V600E mutation, but it causes skin disorders such as dry skin with high frequency. As one of the factors causing skin dryness is a decrease in sebum production due to sebaceous gland dysfunction, we examined whether vemurafenib regulated the production and accumulation of sebum in hamster sebocytes. Vemurafenib dose- and time-dependently decreased the production and accumulation of sebum in DHT-differentiated hamster sebocytes. In addition, the DHT-augmented gene expressions of SCD-1, DGAT-1 and PLIN-1, which are involved in sebum production and accumulation in sebaceous glands, were suppressed by vemurafenib in hamster sebocytes. Unexpectedly, vemurafenib facilitated ERK phosphorylation in hamster sebocytes. In addition, DHT augmented the phosphorylation of ERK, under which vemurafenib synergistically enhanced the DHT-augmented phosphorylation. The enhanced ERK phosphorylation was no longer detectable by adding an ERK inhibitor, U0126. On the other hand, as mTOR plays an important role in the regulation of sebum production, the phosphorylation of Akt and 4EBP1, which are the upstream and downstream molecules in mTOR signalling, respectively, was increased in the DHT-treated hamster sebocytes. Vemurafenib inhibited the DHT-augmented 4EBP1 phosphorylation, which was no longer detectable in the presence of U0126. Furthermore, the suppression of the DHT-augmented sebum production and accumulation by vemurafenib was restored to their levels in DHT alone upon the U0126 treatment. Thus, these results provide novel evidence that vemurafenib suppresses sebum production and accumulation by the vemurafenib-activated ERK signalling that inhibits the Akt/mTOR pathway in DHT-differentiated hamster sebocytes.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853827","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}