Experimental Dermatology最新文献

{"title":"Construction of ceRNA Network and Disease Diagnosis Model for Keloid Based on Tumor Suppressor ERRFI1","authors":"Pengsheng Chen,&nbsp;Qingfu Su,&nbsp;Xingong Lin,&nbsp;Xianying Zhou,&nbsp;Wanting Yao,&nbsp;Xiaxinqiu Hua,&nbsp;Yanyan Huang,&nbsp;Rongrong Xie,&nbsp;Huiyong Liu,&nbsp;Chaoyang Wang","doi":"10.1111/exd.70004","DOIUrl":"https://doi.org/10.1111/exd.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study is to identify the key biomarker of keloid (KD) with significant diagnostic value and to construct the related competing endogenous RNA (ceRNA) network and disease diagnostic model to provide new ideas for the early diagnosis and prevention of KD. Public databases were used to identify the key gene of KD. Enrichment analysis and immune cell infiltration (ICI) analysis revealed its functional and immune characteristics. Then, a ceRNA network was constructed to explore the potential pathways of it. Random forest (RF) analysis was applied to construct a predictive model for the disease diagnosis of KD. Finally, immunohistochemistry (IHC) and RT-qPCR were used to verify the differential expression of key gene. <i>ERRFI1</i> was identified as a key biomarker in KD and was lowly expressed in KD. The ceRNA network revealed that <i>H0TAIRM1-has-miR-148a-3p-ERRFI1</i> may be a potential pathway in KD. Finally, a 2-gene diagnostic prediction model (<i>ERRFI1, HSD3B7</i>) was constructed and externally validated and the results suggested that the model had good diagnostic performance. <i>ERRFI1</i> is a downregulated gene in KD and is expected to be a promising predictive marker and disease diagnostic gene. ICI may play a role in the progression of KD. The ceRNA network may provide new clues to the potential pathogenesis of KD. Finally, the new KD diagnostic model could be an effective tool for assessing the risk of KD development.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674210","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":"Lysophosphatidylcholine Acyltransferase 2 Contributes to Increased Allergic and Irritant Inflammation in Mice","authors":"Midori Kawasaki-Nagano,&nbsp;Risa Tamagawa-Mineoka,&nbsp;Tomoki Kurioka,&nbsp;Yukiyasu Arakawa,&nbsp;Mari Nakanishi,&nbsp;Megumi Kishida,&nbsp;Hiromi Nishigaki,&nbsp;Tomomi Hashidate-Yoshida,&nbsp;Hideo Shindou,&nbsp;Norito Katoh","doi":"10.1111/exd.70015","DOIUrl":"10.1111/exd.70015","url":null,"abstract":"<div>\u0000 \u0000 <p>Platelet-activating factor (PAF) is an important chemical mediator in the field of inflammation, but its function in the skin is unclear. To unravel the role of PAF, we focused on lysophosphatidylcholine acyltransferase 2 (LPCAT2 also called LPLAT9), a biosynthetic enzyme involved in PAF production, and investigated the role of PAF in allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). We measured the amount of PAF in the skin and investigated the ear swelling responses and leukocyte infiltration into the skin following the application of 2,4,6-trinitro-1-chlorobenzene (TNCB) or croton oil in wild-type (WT) and <i>LPCAT2</i> knockout (<i>LPCAT2</i>-KO) mice. The amount of PAF was increased in the skin of WT mice after TNCB or croton oil application but not detected in <i>LPCAT2</i>-KO mice. The ear swelling response was decreased in <i>LPCAT2</i>-KO mice compared with that in WT mice. In the ACD model, the numbers of lymphocytes, eosinophils, macrophages, mast cells and neutrophils were smaller in <i>LPCAT2</i>-KO mice than in WT mice. In the ICD model, the ear swelling response was also decreased in <i>LPCAT2</i>-KO mice compared with that in WT mice. When double staining of each inflammatory cell type and LPCAT2 was performed in ACD tissue, marked co-staining of the eosinophil marker and LPCAT2 was observed. In addition, LPCAT2 expression was observed in the epidermis. These results indicate that PAF is involved in the infiltration of several cell types into the sites of allergic and non-allergic skin inflammation. Furthermore, eosinophils and keratinocytes are primarily responsible for PAF production in skin inflammation.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603634","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":"Disabled 2 (Dab2) Regulates Tumour Progression in Skin Squamous Cell Carcinoma","authors":"Sayoni Roy,&nbsp;Darshan Mehta,&nbsp;Suruchi Sawant,&nbsp;Sanjeev K. Waghmare","doi":"10.1111/exd.70009","DOIUrl":"10.1111/exd.70009","url":null,"abstract":"<p>Dab2 is an endocytic adaptor protein involved in various physiological processes and signaling pathways. Dab2 is deregulated in various cancers; however, its role in skin squamous cell carcinoma ( SCC) has not been elucidated yet. In the present study, we used the DMBA/TPA induced murine skin carcinogenesis model to examine the role of Dab2 in skin tumour progression. We generated tamoxifen inducible Dab2 conditional knockout system for our study. Loss of Dab2 led to delayed papilloma initiation and reduced papilloma burden. Delayed papilloma initiation was due to reduce proliferative potential of the papillomas due to Dab2 loss. Furthermore, while the WT papillomas progressed to SCC, the papillomas formed in Dab2 cKO mice failed to undergo malignant conversion to SCC. Dab2 cKO tumours showed reduced expression of K8, a marker for aggressive tumour. Moreover, Dab2 ckO tumours failed to undergo EMT as shown by reduced expression of Vimentin and Twist1. Dab2 cKO tumours also showed reduced expression of Sox2, a stem cell marker. Furthermore, qPCR analysis showed upregulation of Dab2 expression in the human skin cancer cell lines as compared to normal human skin keratinocytes. In patients, TCGA data analysis of skin cancer melanoma (SKCM) showed a trend where high levels of Dab2 correlated with poor overall survival. The present study shows that Dab2 promotes tumour progression in skin SCC.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581748","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":"Neurofibromatosis Type 1 Patients With Epilepsy: A Comprehensive Analysis of Demographics, Comorbidities and Healthcare Outcomes","authors":"Nilesh Kodali,&nbsp;Audrey Terrany,&nbsp;Keshav D. Kumar,&nbsp;Shae Chambers,&nbsp;Shivkar Amara,&nbsp;Robert A. Schwartz","doi":"10.1111/exd.70011","DOIUrl":"10.1111/exd.70011","url":null,"abstract":"<p>Neurofibromatosis Type 1 (NF1) is the most common neurocutaneous disorder in the United States. Due to a nonfunctional mutation in the NF1 gene, the disorder may initially present with café-au-lait spots and later numerous neurofibromas across the body. Epilepsy is a rare comorbidity of NF1, with an incidence of just 4%–7%. While abnormal electroencephalograms have been seen in up to 25% of NF1 patients, very few studies have investigated the association between epilepsy and the NF1 patient profile. This study was aimed at evaluating the associations between epilepsy and demographics, comorbidities and healthcare outcomes in NF1 patients. The 2017 National Inpatient Sample (NIS) database was retrospectively queried for patients with NF1 using ICD-10 PCS codes. Chi-square tests were used in univariable analysis to compare patients within this cohort with and without epilepsy. Regression analysis was used in multivariable analysis to identify comorbidities that were predictors of epilepsy and the effect of comorbidities on outcomes. 4635 patients with NF1 were identified, of which 655 (14.1%) had epilepsy and 3980 (85.9%) did not. The NF1 patient population with epilepsy was largely comprised of White males of lower household income in larger urban/teaching hospitals and who used Medicare or Medicaid. Multivariable logistic regression revealed that malignant brain neoplasms, paralytic ileus, scoliosis, pregnancy complications, paralysis, other neurological disorders, metastatic cancer, coagulopathy, drug abuse and hypertension were predictors of developing epilepsy in NF1 patients. Additionally, epilepsy in NF1 patients was associated with a shorter length of stay, lower total charges and fewer total procedures.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581871","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":"Incontinence-Associated Dermatitis-Like Skin Changes Induced by the Application of Absorbent Pads Containing Bacteria and Artificial Urine in Rats","authors":"Ai Horinouchi,&nbsp;Yuko Mugita,&nbsp;Sanai Tomida,&nbsp;Chihiro Takizawa,&nbsp;Daijiro Haba,&nbsp;Hiromi Sanada,&nbsp;Gojiro Nakagami","doi":"10.1111/exd.70013","DOIUrl":"https://doi.org/10.1111/exd.70013","url":null,"abstract":"<p>Incontinence-associated dermatitis (IAD) is one of the most serious complications in older people with incontinence. Controlling urine property in absorbent pads could be effective for preventing IAD caused by bacterial urine. However, no animal model has been established to evaluate their effectiveness. This study aimed to induce IAD-like skin changes using absorbent pads containing bacterial urine and to confirm their pathophysiology in rats. Hairless Wistar Yagi rats were divided into the bacteria-containing urine (BU) and the bacteria-free urine (U) groups. A 10-h-attachment of absorbent pads containing artificial urine with/without bacteria to the skin pretreated with sodium lauryl sulfate was performed repeatedly for 5 days. Macroscopic findings and skin barrier function were examined every day, and histological changes, inflammatory responses and bacterial quantification in tissue samples were examined on Day 5. The BU group exhibited significant skin redness from Day 3, significant elevation of transepidermal water loss from Day 1, and histological changes, including significantly thickened epidermis, abnormal keratinocyte differentiation and erythrocyte leakage. Inflammation, confirmed by higher myeloperoxidase-positive cells, elevated tumour necrosis factor-α expression, and vascular endothelial damage, indicated by CD31 and pentraxin 3-positive cells, were observed in the BU group. The bacterial quantification showed no significant difference between the groups. IAD-like skin changes including histological changes and inflammation were suggested to be caused by urine properties altered by bacteria. This study proposed a new animal model for evaluating the effectiveness of absorbent pads in controlling the urine properties of bacterial urine on preventing IAD.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142579732","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":"NEDD4L Inhibits the Proliferation and Migration of Keloid Fibroblasts by Regulating YY1 Ubiquitination-Mediated Glycolytic Metabolic Reprogramming","authors":"Jun Jin,&nbsp;Kai Wang,&nbsp;Chenxi Lu,&nbsp;Chenghao Yao,&nbsp;Feng Xie","doi":"10.1111/exd.70008","DOIUrl":"10.1111/exd.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Keloid scarring is a complex fibroproliferative disorder characterised by excessive fibroblast proliferation. Inhibition of cellular glycolysis effectively suppresses the proliferation of keloid fibroblasts (KFs). Neural precursor cell-expressed developmentally downregulated gene 4-like (NEDD4L), a ubiquitin ligase, regulates cell proliferation in different diseases. This study investigated the effects of NEDD4L on glucose metabolism, proliferation and migration in KFs. Primary KFs were isolated from keloid skin tissues obtained from patients with active-stage keloids. Cell transfection was used to upregulate or downregulate NEDD4L and Yin Yang 1 (YY1) in KFs. Protein expression was assessed by immunohistochemistry and western blotting. The viability, proliferative capacity and migration ability of KFs were evaluated using the MTT method and the EdU and wound healing assays, respectively. The regulatory effect of NEDD4L on YY1 ubiquitination was examined by coimmunoprecipitation. The interaction between YY1 and hexokinase 2 (HK2) was confirmed by a dual-luciferase reporter assay. NEDD4L was downregulated, whereas YY1 and HK2 were highly expressed in keloid tissues compared with normal skin. Overexpression of NEDD4L inhibited the proliferation and migration of KFs. NEDD4L promoted YY1 degradation in KFs by inducing its ubiquitination. Upregulation of YY1 induced glucose consumption and lactate production in KFs via the transcriptional regulation of HK2. Increased expression of YY1 reversed the reduced viability, proliferation, and migration of KFs overexpressing NEDD4L. YY1 also reversed the NEDD4L-induced inhibition of glucose consumption and lactate production in KFs. Additionally, an in vivo study confirmed the inhibitory roles of NEDD4L overexpression and YY1 knockdown in keloid formation. NEDD4L suppressed the viability, proliferation and migration of KFs by regulating YY1 ubiquitination-mediated glycolysis through HK2. These findings suggest a novel regulatory axis, NEDD4L/YY1/HK2, that mediates glucose metabolism in keloid formation.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566492","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":"Dysregulation of Regulatory T Cells and Autoimmune Sequelae in DRESS: Insights From Flow Cytometry and NanoString Analysis","authors":"Suparada Khanaruksombat,&nbsp;Supranee Buranapraditkul,&nbsp;Pattarawat Thantiworasit,&nbsp;Nithikan Suthumchai,&nbsp;Pawinee Rerknimitr,&nbsp;Rangsima Reantragoon,&nbsp;Jettanong Klaewsongkram","doi":"10.1111/exd.70007","DOIUrl":"10.1111/exd.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Drug reactions with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse hypersensitivity reactions with distinct clinical manifestations. Regulatory T (Treg) cells may behave differently in these syndromes, contributing to their diverse clinical features and outcomes. This study compared Treg dynamics between DRESS and SJS/TEN patients during the acute and recovery phases. Flow cytometry quantitatively analysed and defined the immunophenotype of CD4⁺CD25⁺CD127⁻FoxP3⁺ Tregs in blood from DRESS and SJS/TEN patients indicated that Treg percentages were lowest in DRESS patients during the acute phase compared to those in the recovery phase in DRESS patients and the acute phase in SJS/TEN patients. During the acute phase, CTLA-4 expression in Tregs in both DRESS patients with and without autoimmune sequelae was significantly increased, while only DRESS patients without autoimmune sequelae had elevated OX40 expression compared to the healthy controls. High IL-10 expression in Tregs during the acute phase in SJS/TEN patients was also observed. The suppressive function of Tregs was lower in DRESS compared to SJS/TEN, which was determined using a suppression assay by co-culturing autologous Treg and effector T cells. Furthermore, NanoString technology explored mRNA profiles in Tregs. Genes associated with the JAK/STAT pathway were found to be downregulated during the acute phase in DRESS patients who later developed autoimmune sequelae. Our findings evidenced impaired Treg function in DRESS compared to SJS/TEN. The early disturbance of the JAK/STAT pathway may serve as a prognostic marker for autoimmune development in DRESS patients.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563529","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":"Real-World Experience of 3-Year Treatment With Dupilumab: Significant Decrease in Circulating Neutrophils and Eosinophils in Japanese Patients With Atopic Dermatitis","authors":"Hideyuki Nakajima,&nbsp;Masahiro Kamata,&nbsp;Yoshiki Okada,&nbsp;Shoya Suzuki,&nbsp;Makoto Ito,&nbsp;Ayu Watanabe,&nbsp;Shota Egawa,&nbsp;Chika Chijiwa,&nbsp;Azusa Hiura,&nbsp;Yayoi Tomura,&nbsp;Saki Fukaya,&nbsp;Kotaro Hayashi,&nbsp;Atsuko Fukuyasu,&nbsp;Takamitsu Tanaka,&nbsp;Takeko Ishikawa,&nbsp;Yayoi Tada","doi":"10.1111/exd.70010","DOIUrl":"10.1111/exd.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Dupilumab, an anti-interleukin (IL)-4 receptor α-antibody, was approved in 2018 for the treatment of moderate-to-severe atopic dermatitis (AD) in Japan. Although real-world data have accumulated on the effectiveness and safety of dupilumab in patients with AD in the short term, real-world data on its long-term use are limited. In this study, we retrospectively investigated its effectiveness, safety and laboratory data in patients with AD who received dupilumab for 3 years. All adult patients with moderate-to-severe AD who were administered dupilumab between June 2018 and December 2020 and were treated with dupilumab for more than 3 years were included in this study. Sixty Japanese patients with AD (male, 48; female, 12) were included in this study. Their mean age was 36.6 ± 11.0 (standard deviation) years. The mean Eczema Area and Severity Index (EASI) was 29.9 ± 9.2. The clinical severity scales, including Investigator's Global Assessment (IGA), EASI and affected body surface area (BSA), and patient-reported outcomes, such as Dermatology Quality Life Index (DLQI), Patient-Oriented Eczema Measure (POEM) and visual analogue scale (VAS) of pruritus, significantly improved at 3 months, and at 1, 2 and 3 years after initiating dupilumab. The total EASI score significantly decreased by a mean of 66.8% at 3 months, 81.0% at 1 year, 85.3% at 2 years and 90.0% at 3 years after initiating dupilumab. The serum levels of thymus and activation-regulated chemokine (TARC), immunoglobulin E (IgE) and lactate dehydrogenase (LDH) significantly decreased at 1, 2 and 3 years. A slight decrease in circulating neutrophils was observed in patients with AD treated with dupilumab over periods from 3 months to 3 years. The number of circulating eosinophils significantly decreased at 2 and 3 years after initiating dupilumab. The most common adverse event was ocular disorders observed in 23 patients (38.3%). Our study shows the sustained effectiveness and tolerable safety of 3-year usage of dupilumab in Japanese patients with atopic dermatitis. Furthermore, dupilumab decreased neutrophil values at 3 months and later, and reduced the number of circulating eosinophils after long-term use (≧ 2 years).</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563650","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":"Interleukin-33 Deficiency Protects the Skin From Ulcer Formation in an Ischemia-Reperfusion-Induced Decubitus Mouse Model.","authors":"Meijuan Jin, Mayumi Komine, Hidetoshi Tsuda, Miho Sashikawa-Kimura, Susumu Nakae, Sei-Ichiro Motegi, Mamitaro Ohtsuki","doi":"10.1111/exd.70014","DOIUrl":"10.1111/exd.70014","url":null,"abstract":"<p><p>Interleukin-33 (IL-33) is an alarmin released upon epithelial tissue damage. It functions as a nuclear factor for regulating gene expression. We hypothesised that IL-33 is involved in the formation of decubitus ulcers through damaged epidermis. Therefore, this study aimed to clarify the mechanism of IL-33 action in decubitus ulcer formation. IL-33 knockout (KO), soluble stimulation-2 (ST2) transgenic, and wild-type (WT) mice were used to construct an ischemia-reperfusion (I/R) injury as a decubitus model. The ulcer area was significantly reduced in IL-33 KO mice compared to WT mice but was not reduced in ST2 transgenic mice. Anti-IL-33 receptor (transmembrane ST2) antibodies effectively prevented ulcer formation; however, an anti-IL-33 neutralising antibody was ineffective. The number of infiltrating macrophages was higher, while that of neutrophils and mast cells was lower in IL-33 KO mice than in WT mice. The number of M2 macrophages increased in IL-33 KO mice. Characterisation of gene expression levels revealed significantly reduced interleukin-1 beta (IL-1β) and increased C-C motif chemokine ligand 17 expression in IL-33 KO mice. Macrophages isolated from ulcers in WT or IL-33 KO mice stimulated with exogenous IL-33 produced comparable amounts of IL-1β. In conclusion, our study indicates that IL-33 is released in response to I/R injury in the skin, contributing to inflammatory macrophage and mast cell infiltration and stimulation, resulting in IL-1β production and the massive infiltration of effector cells, including neutrophils, which finally induces decubitus ulcer formation. These results suggest that suppressing IL-33 expression could be beneficial for treating early-phase decubitus ulcers.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":"e70014"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647226","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":"Skin Rejuvenation by Modulation of DNA Methylation","authors":"Elke Grönniger,&nbsp;Heiner Max,&nbsp;Frank Lyko","doi":"10.1111/exd.70005","DOIUrl":"10.1111/exd.70005","url":null,"abstract":"<p>Skin aging is driven by a complex set of cellular pathways. Among these, epigenetic mechanisms have garnered particular attention, because of their sensitivity to environmental and lifestyle factors. DNA methylation represents the longest known and best understood epigenetic mechanism. We explain how DNA methylation might function as an interface between the environment and the genome of human skin. Exposures to different environmental factors and lifestyles are known to modulate age-related methylation patterns, as illustrated by their effect on DNA methylation clocks. Human skin provides a particularly well-suited tissue for understanding age-related methylation changes and it has been shown recently that modulation of DNA methylation can induce skin rejuvenation. We explain how the use of mildly demethylating agents can be safeguarded to ensure the specific removal of age-related DNA methylation changes. We also identify important areas of future research, leading to a deeper understanding of the mechanisms that drive epigenetic aging and to the development of further refined intervention strategies.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497756","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}