Experimental Dermatology最新文献

{"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":"33 10","pages":""},"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}

{"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":"33 10","pages":""},"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}

{"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":"33 10","pages":""},"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}

{"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":"33 10","pages":""},"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}

{"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":"33 10","pages":""},"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}

{"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":"33 10","pages":""},"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}

{"title":"Single cell transcriptomics reveals dysregulated immnue homeostasis in different stages in HPV-induced cutaneous squamous cell carcinoma","authors":"Liqing Ding,&nbsp;Lanyuan Peng,&nbsp;Kai Huang,&nbsp;Shunlin Qu,&nbsp;Dongjie Li,&nbsp;Jianhua Yao,&nbsp;Fan Yang,&nbsp;Honglin Zhu,&nbsp;Shuang Zhao","doi":"10.1111/exd.15178","DOIUrl":"10.1111/exd.15178","url":null,"abstract":"<p>In order to explore the huge impact of impaired immnue homeostasis on the occurrence and development of cutaneous squamous cell carcinoma (cSCC), and investigate characterization of the cellular components and their changes which is crucial to understanding the pathologic process of HPV-induced cSCC, we diagnosed and followed up on a very rare HPV-induced cSCC patient who progressed at a very fast rate and transferred to death quickly. We performed single-cell RNA sequencing (scRNA-seq) of 11 379 cells from the skin tissues of this patient with four different skin statuses after HPV infection. Immunofluorescence experiments were used for validation. scRNA-seq identified that CD52⁺ HLA-DOA^- macrophages only existed in paracancerous cutaneous squamous cell carcinoma (pc-cSCC) and cSCC tissue. Besides, immune cells including CD8⁺ exhausted T cells and CD4⁺ regulatory T cells as well as matrix cells like MMP1⁺, and MMP11⁺ fibroblasts were gradually increased. Meanwhile, COMP⁺ ASPN⁺ fibroblasts gradually decreased. Cell interaction analysis revealed enhancement in interactions between monocytes/macrophages, fibroblasts and tumour-specific keratinocytes. scRNA-seq was performed in HPV-induced cSCC for the first time, to explore the correlation between infection and tumour. It is the first time to study the development of tumours from different stages of infection in HPV-induced cSCC. In this study, the tumour itself and the tumour microenvironment were both analysed and explored. And it was validated in clinical samples from different patients. Our findings reveal the dynamic immnue homeostasis from normal skin to cSCC tissue, this alteration might drive HPV-induced cSCC.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389149","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":"Effect of Narrowband Ultraviolet B Phototherapy on Systemic Metabolome in Korean Patients With Psoriasis","authors":"Yufei Li,&nbsp;Yujin Lee,&nbsp;Howard Lee,&nbsp;Seong-Jin Jo,&nbsp;Joo-Youn Cho","doi":"10.1111/exd.15192","DOIUrl":"10.1111/exd.15192","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Psoriasis is a chronic skin disease that increases the risk of developing psoriatic arthritis, cardiovascular disease, and other metabolic disorders. Therefore, understanding the systemic impacts of psoriasis treatments is crucial beyond merely addressing skin lesions. Although phototherapy, particularly narrowband ultraviolet B (nbUVB), is recognised as a safe and effective treatment option for psoriasis, its mechanisms and effects on systemic metabolites are not fully understood. To investigate these potential systemic effects, we conducted an untargeted metabolomic analysis of plasma samples from adult patients with psoriasis who underwent nbUVB phototherapy at least twice a week for a minimum of 8 weeks.&lt;/p&gt;&lt;p&gt;In this single-centre, before-and-after study, 23 patients with moderate-to-severe psoriasis were treated with nbUVB phototherapy at Seoul National University Hospital between 2015 and 2018 (Table S1). Treatments were administered using TL-01 lamps in a UV 7001K cabin (Waldmann, Villingen-Schwenningen, Germany) twice or thrice a week, starting at 400 mJ/cm&lt;sup&gt;2&lt;/sup&gt; and increasing by 10%–20% of the previous dose, with adjustments based on side effects such as erythema, irritation, and itching. The mean duration of phototherapy, mean session count, and cumulative nbUVB dose were 12.0 weeks, 25.0, and 35 423.9 mJ/cm&lt;sup&gt;2&lt;/sup&gt;, respectively. Topical corticosteroids of moderate potency or higher were allowed as needed, whereas no concurrent systemic treatment was administered. For each patient, the psoriasis area and severity index (PASI) score and plasma samples were collected before treatment, as well as on the day of the last UV exposure or the following day. Metabolomic profiling of the plasma samples was performed using an Orbitrap Exploris 120 mass spectrometer, equipped with a Vanquish Flex ultra-high-performance liquid chromatography system (Thermo Fisher Scientific; Waltham, MA, USA).&lt;/p&gt;&lt;p&gt;Following nbUVB phototherapy, the mean PASI score of the patient cohort significantly decreased from 10.6 to 3.3 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, Table S1). Changes in the overall levels of plasma metabolome, including 150 endogenous metabolites annotated with level 2 confidence according to the Metabolomics Standards Initiative, between pre- and post-treatment were subtle (Figure 1A). Five metabolites were found to be significantly changed, which may reflect the mechanism of action of nbUVB phototherapy (Figure 1B). Levels of 4-hydroxy docosahexaenoic acid, an anti-inflammatory metabolite derived from docosahexaenoic acid, decreased after treatment, indicating reduced inflammation [&lt;span&gt;1&lt;/span&gt;]. Levels of creatine, which has been recognised as an antioxidant capable of preventing UVB-induced keratinocyte apoptosis, increased after treatment [&lt;span&gt;2&lt;/span&gt;]. Carnitine, previously reported to be associated with the integral membrane protein CD147 highly expressed in psoriatic skin lesions, showed a similar increasing trend afte","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380406","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":"Proteomic Analysis Reveals Oxidative Phosphorylation and JAK-STAT Pathways Mediated Pathogenesis of Pemphigus Vulgaris","authors":"Yuqi Cheng,&nbsp;Mingming Zhao,&nbsp;CaiHong Zhu,&nbsp;Xianfa Tang,&nbsp;Wenjun Wang,&nbsp;Huayang Tang,&nbsp;Xiaodong Zheng,&nbsp;Zhengwei Zhu,&nbsp;Yujun Sheng,&nbsp;Zaixing Wang,&nbsp;Fusheng Zhou,&nbsp;Jinping Gao","doi":"10.1111/exd.15184","DOIUrl":"10.1111/exd.15184","url":null,"abstract":"<div>\u0000 \u0000 <p>Pemphigus vulgaris (PV) stands as a rare autoimmune bullous disease, while the precise underlying mechanism remains incompletely elucidated. High-throughput proteomic methodologies, such as LC-MS/MS, have facilitated the quantification and characterisation of proteomes from clinical skin samples, enhancing our comprehension of PV pathogenesis. The objective of this study is to elucidate the signalling mechanisms underlying PV through proteomic analysis. Proteins and cell suspension were extracted from skin biopsies obtained from both PV patients and healthy volunteers and subsequently analysed using LC-MS/MS and scRNA-seq. Cultured keratinocytes were treated with PV serum, followed by an assessment of protein expression levels using immunofluorescence and western blotting. A total of 880, 605, and 586 differentially expressed proteins (DEPs) were identified between the lesion vs. control, non-lesion vs. control, and lesion vs. non-lesion groups, respectively. The oxidative phosphorylation (OXPHOS) pathway showed activation in PV. Keratinocytes are the major cell population in the epidermis and highly expressed ATP5PF, ATP6V1G1, COX6B1, COX6A1, and NDUFA9. In the cellular model, there was a notable increase in the expression levels of OXPHOS-related proteins (V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8), along with STAT1, p-STAT1, and p-JAK1. Furthermore, both the OXPHOS inhibitor metformin and the JAK1 inhibitor tofacitinib demonstrated therapeutic effects on PV serum-induced cell separation, attenuating cell detachment. Metformin notably reduced the expression of V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8, p-STAT1, p-JAK1, whereas tofacitinib decreased the expression of p-STAT1 and p-JAK1, with minimal impact on the expression of V-ATP5A, III-UQCRC2, II-SDHB, and I-NDUFB8. Our results indicate a potential involvement of the OXPHOS and JAK-STAT1 pathways in the pathogenesis of PV.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380408","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":"Nrf2 Activation in Keratinocytes: A Central Role in Diabetes-Associated Wound Healing","authors":"Srinivasan Kaussikaa,&nbsp;Murali Krishna Prasad,&nbsp;Kunka Mohanram Ramkumar","doi":"10.1111/exd.15189","DOIUrl":"10.1111/exd.15189","url":null,"abstract":"<p>Wound healing is a complex biological process crucial for tissue repair, wherein keratinocytes play a pivotal role in initiating, sustaining and completing the cascade. Various local and systemic factors, such as lifestyle, age metabolic disorders and vascular insufficiency, can influence this process, and in the context of diabetic wounds, disrupted biological mechanisms, including inflammation, tissue hypoxia, decrease in collagen production along with increased oxidative stress and keratinocyte dysfunction, contribute to delayed healing. During re-epithelialisation, keratinocytes undergo rapid multiplication and migration, forming a dense hyperproliferative epithelial layer that restores the epidermal barrier. Nuclear factor-erythroid 2-related factor (Nrf2), a vital transcription factor, emerges as a central regulator in managing antioxidant proteins and detoxifying enzymes, serving as a guardian against elevated reactive oxygen species (ROS) levels during stress. Nrf2 also orchestrates angiogenesis and anti-inflammatory responses crucial for wound repair. Studies demonstrate that under high-glucose conditions, Nrf2 activation promotes wound healing by enhancing cell proliferation and migration while reducing apoptosis. Nrf2 activators stimulate endogenous antioxidant production, thereby mitigating oxidative stress. Furthermore, Nrf2 upregulation is associated with decreased expression of cytokines such as TNF-α and IL- 6. Recent research underscores the potential of bioactive molecules, including dietary polyphenols, traditional medicinal compounds and pharmacological agents, in activating Nrf2 and preventing diseases such as diabetes due to their robust antioxidative properties. This review aims to investigate the activation of Nrf2 by these bioactive molecules in cultured keratinocytes and animal models, elucidating the key molecular regulatory mechanisms involved in alleviating oxidative stress and facilitating the diabetic wound healing process. Understanding these complex pathways may offer insights into novel therapeutic strategies for enhanced wound healing in diabetes-associated complications.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380407","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}