Experimental Dermatology最新文献

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Implications of the non-neuronal cholinergic system for therapeutic interventions of inflammatory skin diseases 非神经元胆碱能系统对炎症性皮肤病治疗干预的影响
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-18 DOI: 10.1111/exd.15181
Hui-Qi Qu, Charlly Kao, Hakon Hakonarson
{"title":"Implications of the non-neuronal cholinergic system for therapeutic interventions of inflammatory skin diseases","authors":"Hui-Qi Qu,&nbsp;Charlly Kao,&nbsp;Hakon Hakonarson","doi":"10.1111/exd.15181","DOIUrl":"https://doi.org/10.1111/exd.15181","url":null,"abstract":"<p>The pivotal roles of acetylcholine (ACh) in physiological processes encompass both the nervous and non-neuronal cholinergic systems (NNCS). This review delineates the synthesis, release, receptor interactions, and degradation of ACh within the nervous system, and explores the NNCS in depth within skin cells including keratinocytes, endothelial cells, fibroblasts, macrophages, and other immune cells. We highlight the NNCS's essential functions in maintaining epidermal barrier integrity, promoting wound healing, regulating microcirculation, and modulating inflammatory responses. The potential of the NNCS as a therapeutic target for localized ACh regulation in the skin is discussed, though the translation of these findings into clinical practice remains uncertain due to the complexity of cholinergic signalling and the lack of comprehensive human studies. The review progresses to therapeutic modulation strategies of the NNCS, including AChE inhibitors, nicotinic and muscarinic receptor agonists and antagonists, choline uptake enhancers, and botulinum toxin, highlighting their relevance in dermatology. We highlight the impact of the NNCS on prevalent skin diseases such as psoriasis, atopic dermatitis, rosacea, acne, bullous diseases, hyperhidrosis and hypohidrosis, illustrating its significance in disease pathogenesis and therapy. This comprehensive overview aims to enhance understanding of the NNCS's role in skin health and disease, offering a foundation for future research and therapeutic innovation.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451268","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}
引用次数: 0
Identification of Potential Hub Genes in Alopecia Areata 确定脱发症的潜在枢纽基因
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-18 DOI: 10.1111/exd.70002
Runqiu Liu, Longdan Liu, Jiandan Xu, Xiaoting Wen, Yannan Jiang, Qi Qi, Jie Qin, Pingping Qin
{"title":"Identification of Potential Hub Genes in Alopecia Areata","authors":"Runqiu Liu,&nbsp;Longdan Liu,&nbsp;Jiandan Xu,&nbsp;Xiaoting Wen,&nbsp;Yannan Jiang,&nbsp;Qi Qi,&nbsp;Jie Qin,&nbsp;Pingping Qin","doi":"10.1111/exd.70002","DOIUrl":"https://doi.org/10.1111/exd.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Alopecia areata (AA) is an immune-mediated chronic alopecia disease, but its specific pathogenesis is unclear. Gene expression data for AA patients (AAs) and healthy controls (HCs) were retrieved from the GEO database, and the differentially expressed genes (DEGs) between AAs and HCs were identified. Then, GO, KEGG and GSEA analysis were performed. A PPI network for the DEGs was then constructed to screen for hub genes, which were validated by three additional datasets. Subsequently, the potential miRNAs interacting with the hub genes were obtained through TarBase and miRNet. The differentially expressed lncRNAs (DElncRs) were obtained for subcellular localisation analysis, and the DElncRs located in the cytoplasm were further screened to identify miRNAs that interact with them. The shared miRNAs interacting with the hub genes and lncRNAs were used to construct a network of mRNA-miRNA-lncRNA interactions. Lastly, ROC analysis was performed to evaluate the potential diagnostic value of the hub genes and DElncRs identified. A total of 173 DEGs were obtained, mainly enriched in cytokines, chemokines, hair follicle development and hair cycle related signalling pathways. Through PPI screening and validation based on 3 additional datasets, 24 hub genes were finally yielded. Of them, five hub genes were upregulated and the potential miRNAs that interact with these five hub genes were identified. Additionally, 26 DElncRs were obtained, including 9 upregulated lncRNAs located in the cytoplasm that were predicted to interact with the miRNAs. Finally, an mRNA-miRNA-lncRNA regulatory network was constructed using five hub genes, four lncRNAs and their shared five miRNAs. The regulatory relationship between CD8A, mir-185-5p and FOXD2-AS1 might be crucial in AA pathogenesis, with CD8A and FOXD2-AS1 exhibiting diagnostic potential. CD8A and FOXD2-AS1 may serve as potential therapeutic targets in AA.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449140","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}
引用次数: 0
TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis 皮肤鳞状细胞癌中 TROP2 的表达及其治疗意义:免疫组化和功能分析的启示
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-18 DOI: 10.1111/exd.15196
Keiko Tanegashima, Yuka Tanaka, Takamichi Ito, Yoshinao Oda, Takeshi Nakahara
{"title":"TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis","authors":"Keiko Tanegashima,&nbsp;Yuka Tanaka,&nbsp;Takamichi Ito,&nbsp;Yoshinao Oda,&nbsp;Takeshi Nakahara","doi":"10.1111/exd.15196","DOIUrl":"https://doi.org/10.1111/exd.15196","url":null,"abstract":"<p>Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer, but treatments for advanced cases have limited efficacy. Trophoblast cell-surface antigen 2 (TROP2) is a cell-surface protein that is widely expressed in various tumours, where it exerts significant influence over critical processes such as tumour cell growth, apoptosis, migration, invasion and metastasis. Sacituzumab govitecan, an antibody-drug conjugate (ADC) targeting TROP2, is emerging as a promising strategy for anticancer therapy. In this study, we investigated TROP2 expression in cSCC tissues from 51 patients and evaluated its function in the A431 human SCC cell line. Immunohistochemical analysis revealed TROP2 expression on the plasma membrane of cSCC tissues and A431 cells. A431 cells showed sensitivity to sacituzumab govitecan with a significant concentration-dependent decrease in viable cell number. In addition, Knockdown of TROP2 resulted in decreased expression of cyclin D1 and BCL-2, along with reduced cell viability. Knockdown of TROP2 also resulted in decreased expression of vimentin, along with reduced migratory capacity. These findings suggest that TROP2 plays a crucial role in cSCC cell proliferation and migration, and highlight the potential of sacituzumab govitecan as a promising therapeutic option for cSCC.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449138","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}
引用次数: 0
Pharmacological Impacts of Mucopolysacccharide Polyphosphates in the Epidermis Involves Inhibition of Amphiregulin-Mediated Signals in Keratinocytes 粘多糖多磷酸盐对表皮的药理影响涉及抑制角质形成细胞中由安非拉酮介导的信号
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-18 DOI: 10.1111/exd.70000
Ryo Hirase, Tomoyuki Fujita, Tomohiro Miyai, Hiroshi Kawasaki, Haruhiko Koseki
{"title":"Pharmacological Impacts of Mucopolysacccharide Polyphosphates in the Epidermis Involves Inhibition of Amphiregulin-Mediated Signals in Keratinocytes","authors":"Ryo Hirase,&nbsp;Tomoyuki Fujita,&nbsp;Tomohiro Miyai,&nbsp;Hiroshi Kawasaki,&nbsp;Haruhiko Koseki","doi":"10.1111/exd.70000","DOIUrl":"https://doi.org/10.1111/exd.70000","url":null,"abstract":"<p>The epidermis, the most superficial layer of the human skin, serves a critical barrier function, protecting the body from external pathogens and allergens. Dysregulation of epidermal differentiation contributes to barrier dysfunction and has been implicated in the pathology of various dermatological diseases, including atopic dermatitis (AD). Mucopolysaccharide polysulphate (MPS) is a moisturising agent used to treat xerosis in patients with AD. However, its mechanism of action on keratinocytes, the main constituents of the epidermis, remains unclear. In this study, we investigated the effect of MPS on keratinocytes by subjecting adult human epidermal and three-dimensional cultured keratinocytes to MPS treatment, followed by transcriptome analysis. The analysis revealed that MPS treatment enhances keratinocyte differentiation and suppresses proliferation. We focused on amphiregulin (AREG), a membrane protein that belongs to the epidermal growth factor (EGF) family and possesses a heparin-binding domain, as a significant target among the genes altered by MPS. MPS exerted an inhibitory effect directly on AREG, rather than on EGF receptors or other members of the EGF family. Furthermore, AREG leads to a reduction in epidermal barrier function, whereas MPS contributes to barrier enhancement via AREG inhibition. Collectively, these findings suggest that MPS modulates barrier function through AREG inhibition, offering insights into potential therapeutic strategies for skin barrier restoration.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451273","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}
引用次数: 0
The Proportion of Catagen and Telogen Hair Follicles in Occipital Scalp of Male Androgenetic Alopecia Patients: Challenging the Established Dogma 男性雄激素性脱发患者枕部头皮中生长期和退行期毛囊的比例:挑战既定教条
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-18 DOI: 10.1111/exd.70001
Francisco Jimenez, Majid Alam
{"title":"The Proportion of Catagen and Telogen Hair Follicles in Occipital Scalp of Male Androgenetic Alopecia Patients: Challenging the Established Dogma","authors":"Francisco Jimenez,&nbsp;Majid Alam","doi":"10.1111/exd.70001","DOIUrl":"https://doi.org/10.1111/exd.70001","url":null,"abstract":"<p>The hair follicle can cycle throughout a lifetime, undergoing periods of growth (anagen), regression (catagen) and relative quiescence (telogen). The time that a hair follicle spends in each of these stages is crucial to determine the length of hair fibre that it produces. Perturbations in this regard can manifest in various hair diseases such as anagen effluvium, or acute and chronic telogen effluvium. The established ‘dogma’ when considering how many hair follicles there are in each stage has long been that the majority are in anagen (85%–90%), followed by telogen (10%–15%) and catagen (1%–2%). These values are based on various studies using different methodologies such as hair plucking, phototrichograms and histology. However, these methods have flaws when it comes to differentiating between catagen and telogen follicles. We sought to determine the catagen: telogen ratio through the ex vivo stereomicroscopic examination of hundreds of hair follicles removed from the occipital scalp of 14 Caucasian males during routine hair transplantation procedures. Using this methodology, and in agreement with a similar observation by another research group, we found that the percentage of catagen hair follicles was higher (7.5%) than telogen (3.5%) in all patients assessed. Consequently, we believe that the percentage of catagen follicles is clearly underestimated and therefore challenge the current established dogma.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449139","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}
引用次数: 0
Strengthening the Skin Barrier by Using a Late Cornified Envelope 6A-Derived Biomimetic Peptide 使用晚玉米化包膜 6A 衍生的生物仿生肽强化皮肤屏障
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-13 DOI: 10.1111/exd.15191
Mikaël Pancarte, Julie Leignadier, Séverine Courrech, Guy Serre, Joan Attia, Nathalie Jonca
{"title":"Strengthening the Skin Barrier by Using a Late Cornified Envelope 6A-Derived Biomimetic Peptide","authors":"Mikaël Pancarte,&nbsp;Julie Leignadier,&nbsp;Séverine Courrech,&nbsp;Guy Serre,&nbsp;Joan Attia,&nbsp;Nathalie Jonca","doi":"10.1111/exd.15191","DOIUrl":"https://doi.org/10.1111/exd.15191","url":null,"abstract":"<p>Changes in the expression of cornified envelope (CE) components are a hallmark of numerous pathological skin conditions and aging, underlying the importance of this <i>stratum corneum</i> structure in the homeostasis of the epidermal barrier. We performed a detailed characterisation of LCE6A, a member of the Late Cornified Envelope protein family. Immunohistochemical and immunoblot experiments confirmed that LCE6A is expressed late during epidermal differentiation. Crosslinking assays of recombinant LCE6A performed either in situ on human skin sections or in vitro demonstrated that LCE6A is indeed a substrate of transglutaminases and crosslinked to CEs. LCE6A-derived peptides containing a glutamine-lysine sequence retained these properties of the full-length protein and reinforced the mechanical resistance of CE submitted to sonication. We designed P26, a LCE6A-derived biomimetic peptide that similarly reinforced CE in vitro, and evaluated its protective properties ex vivo, on human skin explants, and in two double blind and vehicle-controlled clinical trials. P26 was able to protect the skin from barrier disruption, to limit the damage resulting from a defective barrier, and could improve the signs of aging such as loss of skin firmness and increased skin roughness. Hence, our detailed characterisation of LCE6A as a component of the CE enabled us to develop a LCE6A-derived peptide, biologically active with a new and original mode of action that could be of great interest as a cosmetic ingredient and a pharmacologic agent.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435363","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}
引用次数: 0
Prevalence and Predictors of Inflammatory Arthritis in Hidradenitis Suppurativa 化脓性扁桃体炎炎症性关节炎的发病率和预测因素
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-13 DOI: 10.1111/exd.15194
Sheena Maureen T. Sy, Lihi Eder, Dana Jerome, Chikaodili Obetta, Hayley McKee, Reza Mirza, Elisabeth Pek, Vincent Piguet, Raed Alhusayen
{"title":"Prevalence and Predictors of Inflammatory Arthritis in Hidradenitis Suppurativa","authors":"Sheena Maureen T. Sy,&nbsp;Lihi Eder,&nbsp;Dana Jerome,&nbsp;Chikaodili Obetta,&nbsp;Hayley McKee,&nbsp;Reza Mirza,&nbsp;Elisabeth Pek,&nbsp;Vincent Piguet,&nbsp;Raed Alhusayen","doi":"10.1111/exd.15194","DOIUrl":"https://doi.org/10.1111/exd.15194","url":null,"abstract":"<p>Hidradenitis Suppurativa (HS) is a chronic, debilitating, auto-inflammatory condition often associated with inflammatory arthritis, significantly impacting patients' quality of life. Early diagnosis of both conditions is crucial for optimal management. The objective of this study was to determine the prevalence and factors associated with the development of inflammatory arthritis among HS patients. A cross-sectional study was conducted between November 2021 and February 2023 at an academic dermatology centre in Canada. Adult patients with HS were consecutively sampled, and 52 patients consented to participate and completed assessments. Variables examined included age, sex, HS severity, treatment, ethnicity, family history, lifestyle factors and comorbidities. The main outcomes were rheumatologist-confirmed inflammatory arthritis diagnosis and associated risk factors. Among 52 patients (24 males, 28 females; mean age: 37.4 years), 12 had inflammatory arthritis. Multivariate analysis revealed that Blacks (OR = 0.10, <i>p</i> &lt; 0.001, CI: 0.026–0.343) and Asians (OR = 0.02, <i>p</i> &lt; 0.001, CI: 0.005–0.109) had lower inflammatory arthritis odds compared to Whites. Every 1-year increase in age at HS onset correlated with a 1.17-fold increase in the odds of developing inflammatory arthritis (OR: 1.17, <i>p</i> &lt; 0.001, CI: 1.12–1.24). Smoking (OR = 0.01, <i>p</i> &lt; 0.001, CI: 0.002–0.49), hypertension (OR: 0.23, <i>p</i> = 0.04, CI: 0.057–0.930) and depression (OR: 0.12, <i>p</i> &lt; 0.001, CI: 0.041–0.330) reduced inflammatory arthritis odds. White ethnicity and older age at HS onset were positively associated with inflammatory arthritis, while smoking, hypertension and depression were negatively associated. These findings suggest a distinct subset of HS patients with inflammatory arthritis that warrant further prospective studies. This study contributes to the understanding of inflammatory arthritis in HS patients and emphasises the importance of rheumatology referral during dermatologic clinic visits.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435328","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}
引用次数: 0
Mental Health, Sleep and General Health Among Individuals With Dermatologic Conditions: A US Population-Based Study Using the National Health and Nutrition Examination Survey (NHANES) 皮肤病患者的心理健康、睡眠和总体健康状况:利用全国健康与营养调查 (NHANES) 开展的一项基于美国人口的研究
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-13 DOI: 10.1111/exd.15195
Shawheen J. Rezaei, Michael L. Chen, Jiyeong Kim, Eleni Linos
{"title":"Mental Health, Sleep and General Health Among Individuals With Dermatologic Conditions: A US Population-Based Study Using the National Health and Nutrition Examination Survey (NHANES)","authors":"Shawheen J. Rezaei,&nbsp;Michael L. Chen,&nbsp;Jiyeong Kim,&nbsp;Eleni Linos","doi":"10.1111/exd.15195","DOIUrl":"https://doi.org/10.1111/exd.15195","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435329","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}
引用次数: 0
Lesional Psoriasis is Associated With Alterations in the Stratum Corneum Ceramide Profile and Concomitant Decreases in Barrier Function 皮损型银屑病与角质层神经酰胺谱的改变和屏障功能的降低有关。
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-09 DOI: 10.1111/exd.15185
Jannik Rousel, Catherine Mergen, Menthe E. Bergmans, Naomi B. Klarenbeek, Tessa Niemeyer-van der Kolk, Martijn B. A. van Doorn, Joke A. Bouwstra, Robert Rissmann, the Next-Generation ImmunoDermatology Consortium (NGID)
{"title":"Lesional Psoriasis is Associated With Alterations in the Stratum Corneum Ceramide Profile and Concomitant Decreases in Barrier Function","authors":"Jannik Rousel,&nbsp;Catherine Mergen,&nbsp;Menthe E. Bergmans,&nbsp;Naomi B. Klarenbeek,&nbsp;Tessa Niemeyer-van der Kolk,&nbsp;Martijn B. A. van Doorn,&nbsp;Joke A. Bouwstra,&nbsp;Robert Rissmann,&nbsp;the Next-Generation ImmunoDermatology Consortium (NGID)","doi":"10.1111/exd.15185","DOIUrl":"10.1111/exd.15185","url":null,"abstract":"<p>Psoriasis is an inflammatory skin disease associated with an impaired skin barrier. The skin barrier function is dependent on the extracellular lipid matrix which surrounds the corneocytes in the stratum corneum. Ceramides comprise essential components of this matrix. Alterations in the stratum corneum ceramide profile have been directly linked to barrier dysfunction and might be an underlying factor of the barrier impairment in psoriasis. In this study, we investigated the ceramide profile and barrier function in psoriasis. Lesional and non-lesional skin of 26 patients and 10 healthy controls were analysed using in-depth ceramide lipidomics by liquid chromatography-mass spectrometry. Barrier function was assessed by measuring transepidermal water loss. Lesional skin showed a significant decrease in the abundance of total ceramides with significant alterations in the ceramide subclass composition compared to control and non-lesional skin. Additionally, the percentage of monounsaturated ceramides was significantly increased, and the average ceramide chain length significantly decreased in lesional skin. Altogether, this resulted in a markedly different profile compared to controls for lesional skin, but not for non-lesional skin. Importantly, the reduced barrier function in lesional psoriasis correlated to alterations in the ceramide profile, highlighting their interdependence. By assessing the parameters 2 weeks apart, we are able to highlight the reproducibility of these findings, which further affirms this connection. To conclude, we show that changes in the ceramide profile and barrier impairment are observed in, and limited to, lesional psoriatic skin. Their direct correlation provides a further mechanistic basis for the concomitantly observed impairment of barrier dysfunction.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389148","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}
引用次数: 0
Transcriptomic Analysis of Early-Stage Basal Cell Carcinomas in Murine Skin Following Topical Treatments With Ablative Fractional Laser and Vismodegib 用烧蚀点阵激光和 Vismodegib 局部治疗后早期小鼠皮肤基底细胞癌的转录组分析
IF 3.5 3区 医学
Experimental Dermatology Pub Date : 2024-10-09 DOI: 10.1111/exd.15187
Kristian Kåber Pedersen, Merete Hædersdal, Uffe Høgh Olesen, Thomas Litman
{"title":"Transcriptomic Analysis of Early-Stage Basal Cell Carcinomas in Murine Skin Following Topical Treatments With Ablative Fractional Laser and Vismodegib","authors":"Kristian Kåber Pedersen,&nbsp;Merete Hædersdal,&nbsp;Uffe Høgh Olesen,&nbsp;Thomas Litman","doi":"10.1111/exd.15187","DOIUrl":"10.1111/exd.15187","url":null,"abstract":"<p>Recent studies have demonstrated that ablative fractional laser (AFL) can inhibit the hedgehog pathway, enhance immune infiltration and clear basal cell carcinomas (BCCs) in murine models. In this study, we applied RNA sequencing to further characterise the impact of AFL on the transcriptome of murine skin containing early-stage microscopic BCCs, contrasting it with the effects of topical application of the hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation (significantly upregulated genes: 277, significantly downregulated genes: 24). Characterisation of these genes with Ingenuity Pathway Analysis showed that tumour induction was associated with activation of BCC and Sonic Hedgehog signalling. Both AFL and vismodegib treatments reversed these changes, with vismodegib demonstrating superior performance by reversing most of the upregulated genes (AFL: 59/277; vismodegib: 180/277). Surprisingly, Ingenuity Pathway Analysis also revealed that both AFL and vismodegib treatments caused considerable immune cell infiltration. Based on gene set enrichment analysis and cell type deconvolution, AFL treatment resulted in the largest immune cell recruitment, which for both treatments primarily consisted of infiltrating neutrophils, macrophages and monocytes. In conclusion, the distinct effects observed in BCC skin following AFL and vismodegib treatment suggest key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining the effect of AFL on the immune system with other topical treatments.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389150","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}
引用次数: 0
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