Journal of dermatological science最新文献

{"title":"Aberrant fumarate metabolism links interferon release in diffuse systemic sclerosis.","authors":"Thomas Steadman, Steven O'Reilly","doi":"10.1016/j.jdermsci.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.01.002","url":null,"abstract":"<p><strong>Background: </strong>Systemic Sclerosis (SSc) is an idiopathic rheumatic inflammatory disease that is characterised by inflammation and skin fibrosis. Type I interferon is significantly elevated in the disease.</p><p><strong>Objective: </strong>The objective of this study is to determine the role of the TCA cycle metabolite fumarate in SSc.</p><p><strong>Methods: </strong>CD14 + cells were isolated from 12 SSc patients and healthy controls. Fumarate hydratase and Interferon dependant genes were quantified by qPCR. In vitro inhibition of STING using a small molecule STING inhibitor and enforced mitophagy was induced in vitro and IFN-β release was quantified. VDAC1 inhibitor was used to determine the role of mt DNA release in IFN-β induction. In whole skin biopsies fumarate and succinate was quantified.</p><p><strong>Results: </strong>Fumarate Hydratase is significantly reduced in SSc monocytes. Type I interferon is also elevated in monocytes from SSc donors compared to controls. The mitochondrial-specific stress marker GDF-15 was significantly elevated in SSc monocytes. Blockade of the cGAS-STING pathway chemically reduced interferon-β release and induced mitophagy also retarded release of the cytokine in response to LPS stimulation. Inhibition of VDAC1 mitigated IFN-β, as did the depletion of mitochondria in cells. Furthermore, the itaconate derivative 4-octyl itaconate reduced IFN-β induction in SSc monocytes, that was downstream of mitochondrial nucleic acid release. Fumarate, but not succinate was elevated in whole skin biopsies.</p><p><strong>Conclusion: </strong>Fumarate metabolism links interferon release in SSc and may underlie the aberrant expression of interferon in SSc via cytosolic DNA released from mitochondria.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unfolded protein response modulates Tyrosinase levels and melanin production during melanogenesis.","authors":"Akari Yamazaki, Issei Omura, Yasunao Kamikawa, Michihiro Hide, Akio Tanaka, Masayuki Kaneko, Kazunori Imaizumi, Atsushi Saito","doi":"10.1016/j.jdermsci.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.01.001","url":null,"abstract":"<p><strong>Background: </strong>Melanocytes protect the body from ultraviolet radiation by synthesizing melanin. Tyrosinase, a key enzyme in melanin production, accumulates in the endoplasmic reticulum (ER) during melanin synthesis, potentially causing ER stress. However, regulating ER function for melanin synthesis has been less studied than controlling Tyrosinase activity.</p><p><strong>Objective: </strong>This study investigates the regulatory mechanisms of melanin production, focusing on ER stress and the ER stress-induced response.</p><p><strong>Methods: </strong>B16 mouse melanoma cells induced to undergo melanogenesis were treated with unfolded protein response (UPR) inhibitors or chemical chaperones, and their effects on melanogenesis were analyzed.</p><p><strong>Results: </strong>During melanogenesis in B16 cells stimulated by alpha-melanocyte-stimulating hormone (α-MSH), ER stress and UPR activation occurred, accompanied by increased Tyrosinase protein. Reducing IRE1 and ATF6 branch activity lowered melanin levels, while chemical chaperone treatment restored melanin production and increased Tyrosinase levels.</p><p><strong>Conclusion: </strong>UPR activation, linked to elevated Tyrosinase levels, influences melanin production during melanogenesis. Modulating UPR can regulate melanin synthesis and provides a potential new approach for treating pigmentation disorders.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"The cumulative effect of compound heterozygous variants in TRPV3 caused Olmsted syndrome\" [J. Dermatol. Sci. (2024) S0923-1811(24)00214-7].","authors":"Ran Mo, Xiaoqi Ma, Linghan Hu, Yingjian Tan, Lei Qiang, Yong Yang, Xiaoping Wang, Zhiming Chen","doi":"10.1016/j.jdermsci.2024.11.003","DOIUrl":"10.1016/j.jdermsci.2024.11.003","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":"18"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of immunological tests for detecting autoantibodies in patients with lamina lucida-type linear IgA bullous dermatosis.","authors":"Masahiro Tsutsumi, Hiroshi Koga, Kwesi Teye, Norito Ishii, Takekuni Nakama","doi":"10.1016/j.jdermsci.2024.12.001","DOIUrl":"10.1016/j.jdermsci.2024.12.001","url":null,"abstract":"<p><strong>Background: </strong>In the diagnosis of linear IgA bullous dermatosis (LABD), detection of IgA at the epidermal basement membrane zone and circulating IgA autoantibodies are essential. The disease has two subtypes, lamina lucida-type and sublamina densa-type, with 120 kDa LAD-1 and 97 kDa LABD97 as major autoantigens for lamina lucida-type. Normal human epidermal keratinocytes (NHEK) and HaCaT cells are widely used for immunoblotting (IB) in the diagnosis process, but they do not provide high sensitivity and semiquantitative analysis.</p><p><strong>Objective: </strong>To develop a more sensitive and convenient method for detecting IgA antibodies in lamina lucida-type LABD patients.</p><p><strong>Methods: </strong>The expressions of LAD-1 and LABD97 in lysates and culture supernatants from Ker-CT, HaCaT, DJM-1, and NHEK were compared. The sensitivity of IBs using concentrated culture supernatants of HaCaT and Ker-CT and ELISAs using several recombinant proteins (RPs) corresponding to BP180 ectodomain were compared using 55 sera from LABD patients.</p><p><strong>Results: </strong>In culture supernatant, Ker-CT expressed higher amounts of LAD-1 and LABD97. IBs using concentrated culture supernatant of HaCaT and Ker-CT showed 43 % and 46 % positivity to sera from LABD patients, respectively. In ELISAs, the RP of amino acids 490-1421 of BP180 showed the highest positivity (80.0 %) among several proteins. Additionally, this ELISA showed reduced OD values in LABD and related diseases patients' sera at remission.</p><p><strong>Conclusion: </strong>The ELISA using the RP coding amino acids 490-1421 of BP180 is useful for identifying IgA antibodies and monitoring disease activity in lamina lucida-type LABD patients.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":"2-7"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of TLR2 in keratinocytes activates the MAPK pathway and plays a role in the pathogenesis of hidradenitis suppurativa.","authors":"Haini Zhang, Yi Li, Xiaodong Lai, Chong Zhang, Zhongshuai Wang, Yan Yang, Baoxi Wang, Yan Yan","doi":"10.1016/j.jdermsci.2024.11.002","DOIUrl":"10.1016/j.jdermsci.2024.11.002","url":null,"abstract":"<p><strong>Background: </strong>Mutations in gamma-secretase complex (GSC) genes are associated with hidradenitis suppurativa (HS), and toll-like receptor (TLR) 2 is elevated in HS lesions. However, it remains unclear whether TLR2 is upregulated in the skin lesions of patients with HS with GSC gene variants, and the role of its upregulation in the pathogenesis of this disease are unknown.</p><p><strong>Objective: </strong>To investigate the role of TLR2 upregulation in NCSTN and PSENEN knockdown keratinocytes.</p><p><strong>Methods: </strong>Human immortalized keratinocyte line (HaCaTs) was treated with potent short-hairpin RNA targeting NCSTN or PSENEN. RNA sequencing was used to assess the effects of PAM2CSK4 treatment on gene expression in HaCaT cells. Altered signaling pathways were confirmed in both HaCaT cells, as well as in skin lesions from patients with HS and in Ncstn keratinocyte-specific knockout (Ncstn^ΔKC) mice.</p><p><strong>Results: </strong>TLR2 agonist stimulation exacerbated the increased phosphorylation levels of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase (MAPK) in NCSTN- and PSENEN- knockdown keratinocytes. Similar findings were observed in skin lesions from patients with HS and Ncstn^ΔKC mice.</p><p><strong>Conclusion: </strong>Novel variations were identified within the GSC gene in Chinese patients with HS. Moreover, our study indicates that TLR2/MAPK signaling pathways play a key role in the pathogenesis of HS associated with GSC gene mutations and represent a crucial therapeutic target.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":"8-17"},"PeriodicalIF":4.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Fli1 deletion on B cell populations: A focus on age-associated B cells and transcriptional dynamics.","authors":"Kentaro Awaji, Sayaka Shibata, Asumi Koyama, Toyoki Yamamoto, Yuki Fukui, Satoshi Toyama, Jun Omatsu, Yuta Norimatsu, Tetsuya Ikawa, Yusuke Watanabe, Takuya Miyagawa, Takashi Yamashita, Yukiteru Nakayama, Maria Trojanowska, Shinichi Sato, Yoshihide Asano","doi":"10.1016/j.jdermsci.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2024.12.003","url":null,"abstract":"<p><strong>Background: </strong>Altered Fli1 expression is associated with various autoimmune diseases, yet its impact on B cells remains unexplored.</p><p><strong>Objective: </strong>This study investigated the direct effects of Fli1 depletion on B cell populations, focusing on age-associated B cells (ABCs).</p><p><strong>Methods: </strong>Splenocytes of Fli1 BcKO (Cd19-Cre^+/-; Fli1^flox/flox) and Cd19-Cre^+/- mice were analyzed flow cytometrically. Transcriptional/epigenetic profiles of Cd11b⁺Cd11c⁺ ABCs were examined by RNA-sequencing and ATAC-sequencing.</p><p><strong>Results: </strong>Fli1 BcKO mice displayed a notable reduction in follicular and marginal zone B cells, with a concurrent rise in newly formed B cells compared to Cd19-Cre^+/- mice. Additionally, a striking increase in B-1 B cells, as well as Cd11b⁺Cd11c⁺ or T-bet⁺Cd11c⁺ ABCs, was observed in Fli1 BcKO mice. Furthermore, these mice exhibited elevated Cd138 levels in follicular B cells. Conducting transcriptional analyses of Fli1-depleted ABCs unveiled upregulated genes associated with cell-cell adhesion, coupled with downregulated genes linked to cell activation or immune responses. Exploring the chromatin landscape found that Fli1 depletion dysregulated the chromatin accessibility of the interferon regulatory factor family, implying potential roles in autoimmunity.</p><p><strong>Conclusion: </strong>These findings suggest complex modulations of B cell populations and immune-related gene expression due to Fli1 deficiency, shedding light on its involvement in autoimmune processes.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X7R-primed keratinocytes are susceptible to apoptosis via GPCR-Gβγ-pERK signal pathways.","authors":"Tomoki Nishiguchi, Haruna Kimura, Yuki Saito, Takeaki Ozawa, Riichiro Abe, Akito Hasegawa","doi":"10.1016/j.jdermsci.2024.10.001","DOIUrl":"10.1016/j.jdermsci.2024.10.001","url":null,"abstract":"<p><strong>Background: </strong>Cell death constitutes a pivotal biological phenomenon essential for the preservation of homeostasis within living organisms. In the context of maintaining a functional skin barrier, keratinocytes exert positively and negatively control cell death signals. However, in patients with severe drug eruptions, anomalous overexpression of the formyl peptide receptor 1 (FPR1) in keratinocytes elicits a distinctive mode of cell death known as necroptosis, thereby suffering a loss of the skin barrier. The precise molecular mechanisms connecting FPR1 activation to this cell death remain unclear.</p><p><strong>Objective: </strong>We have investigated the intracellular signal transduction cascade governing FPR1-mediated cell death in cultured keratinocytes.</p><p><strong>Methods: </strong>We used HaCaT cells as a model keratinocyte. The expression of FPR1 was detected with qPCR. The presence of cell death events was monitored through live-cell fluorescent staining and LDH release assays. Furthermore, the phosphorylation of ERK was assessed via Western blot analysis. Intracellular signal pathways were investigated using specific inhibitors.</p><p><strong>Results: </strong>Ligand stimulation of an endogenous ion channel, purinergic receptor P2X7 (P2X7R), increased the FPR1 expression level. This upregulated FPR1 demonstrated functional competence in the phosphorylation of downstream MAP kinase and the initiation of cell death. Notably, this cell death was ameliorated upon the administration of inhibitors targeting Gβγ, ERK, and caspases.</p><p><strong>Conclusion: </strong>The induction and stimulation of FPR1 initiated apoptosis in keratinocytes via the Gβγ-pERK signaling pathway. Our findings postulate that the downstream components of FPR1 represent an alternative therapeutic target for preventing unintended keratinocyte cell death.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":"90-99"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A carbamazepine metabolite activates NLRP3 and controls skin homing of CD8⁺ T-cells in SJS/TEN.","authors":"Chen Zhang, Pei Qiao, JieYu Zhang, YiXin Luo, ChunYing Xiao, ShengXian Shen, Akio Hasegawa, HongJiang Qiao, Gang Wang, Riichiro Abe, Meng Fu","doi":"10.1016/j.jdermsci.2024.10.003","DOIUrl":"10.1016/j.jdermsci.2024.10.003","url":null,"abstract":"<p><strong>Background: </strong>Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions with extensive keratinocyte death. Carbamazepine (CBZ), the most commonly implicated drug in SJS/TEN, is metabolized by the cytochrome P450 enzyme 3A4 (CYP3A4) into carbamazepine-10,11-epoxide (CBZE) in the liver. While CD8⁺ cytotoxic T cells play an important role in SJS/TEN, the underlying mechanism of exuberant immune response by CD8⁺ T cells in these conditions remains incompletely understood.</p><p><strong>Objectives: </strong>To examine the expression of NLRP3 inflammasome and their skin migration in CBZE-induced SJS/TEN.</p><p><strong>Methods: </strong>The expression of the NLRP3 inflammasome complex in skin lesions, sera, and blister fluids of SJS/TEN patients were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay. NLRP3 formation and CD8⁺ T cell activation status and their functions were examined by immunoblotting, immunofluorescence, and chemotaxis assays.</p><p><strong>Results: </strong>The expression of the NLRP3 inflammasome complex was greatly increased in skin lesions of SJS/TEN patients. Moreover, IL-1β and IL-18 levels in sera and blister fluids of SJS/TEN patients were approximately 3-fold higher than those in healthy individuals, with a linear correlation between IL-1β levels and disease activity. CBZE induced NLRP3 inflammasome formation, upregulated CXCL9/CXCL10 levels, and activated CD8⁺ cytotoxic T cell functions via IL-1β/IL-1R or IL-18/IL-18R signaling in SJS/TEN keratinocytes, which promoted CD8⁺ cytotoxic T cell migration in SJS/TEN patients.</p><p><strong>Conclusion: </strong>This study showed that CBZE promoted NLRP3 inflammasome formation and strengthened the activation and function of CD8⁺ cytotoxic T cells in the skin, which contributed to the initiation and progression of SJS/TEN.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":"80-89"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cumulative effect of compound heterozygous variants in TRPV3 caused Olmsted syndrome.","authors":"Ran Mo, Xiaoqi Ma, Linghan Hu, Yingjian Tan, Lei Qiang, Yong Yang, Xiaoping Wang, Zhiming Chen","doi":"10.1016/j.jdermsci.2024.10.005","DOIUrl":"10.1016/j.jdermsci.2024.10.005","url":null,"abstract":"<p><strong>Background: </strong>Olmsted syndrome (OS) is a rare genodermatosis predominantly inherited in an autosomal dominant manner, typically arising from gain-of-function (GOF) variants in the transient receptor potential channel vanilloid 3 (TRPV3) gene.</p><p><strong>Objective: </strong>This study aims to investigate potential mechanisms underlying OS in two cases presenting with an autosomal recessive inheritance pattern.</p><p><strong>Methods: </strong>Next-generation sequencing panel was employed to identify TRPV3 variants. TRPV3 plasmids carrying specific point variations were generated and transiently transfected into HEK293T cells. Electrophysiological patch-clamp techniques were utilized to record voltage-activated and ligand-activated currents. Celltiter-Glo luminescent assay was employed to analyze the cell viabilities.</p><p><strong>Results: </strong>Compound heterozygous variants, c.1563 G>C (p.W521C) and c.1376 C>T (p.S459L), as well as c.1773 G>C (p.L591F) and c.2186 G>A (p.R729Q), were identified in the two OS patients respectively. Electrophysiological analysis of ligand-induced activation of TRPV3 variants demonstrated the closest correlation with clinical manifestations. All four variants displayed GOF channel activity characterized by increased sensitivity. Notably, W521C and L591F exhibited both heightened sensitivity and lower EC50 values for the TRPV3 agonist. Co-transfection with wild-type TRPV3 plasmids significantly rescued these effects. Cells co-transfected with the corresponding compound heterozygous variants exhibited intermediate electrophysiological characteristics.</p><p><strong>Conclusions: </strong>In this study, we present two cases of OS by autosomal-recessive inheritance of TPRV3 variants. This study presents a notable observation of compound heterozygous GOF variants in TRPV3, highlighting their cumulative impact on clinical manifestations. Additionally, we advocate for the use of ligand-dependent ion channel activity assays to assess the pathogenicity of TRPV3 variants in OS.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":"111-119"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide DNA methylation regulated by AHCY through SAM / SAH axis promotes psoriasis pathogenesis.","authors":"Lingxi Liu, Lihao Chen, Yu Hu, Qian Zhang, Kun Chen, Jiaan Zhang","doi":"10.1016/j.jdermsci.2024.10.004","DOIUrl":"10.1016/j.jdermsci.2024.10.004","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disease that affects a significant proportion of the global population. The involvement of S-adenosine homocysteine hydrolase (AHCY) in psoriasis and its impact on DNA methylation have not been extensively studied.</p><p><strong>Objective: </strong>This study aimed to investigate the role of AHCY and its impact on DNA methylation in psoriasis pathogenesis.</p><p><strong>Methods: </strong>In the present study, we investigated the expression of AHCY in psoriatic lesions and assessed its association with the severity of the disease. Moreover, knockdown experiments were conducted to elucidate the impact of AHCY on psoriatic symptoms, keratinocyte proliferation, and aberrant differentiation. Furthermore, alterations in DNA methylation patterns resulting from AHCY knockdown were analyzed.</p><p><strong>Results: </strong>Our findings revealed that AHCY was upregulated in psoriatic lesions and exhibited a positive correlation with disease severity. Knockdown of AHCY alleviated psoriatic symptoms, inhibited keratinocyte proliferation, and prevented abnormal differentiation. Moreover, AHCY knockdown led to reduced levels of DNA methylation and alterations in methylation patterns. Notably, differential methylation was observed at specific gene loci associated with psoriasis-related inflammation.</p><p><strong>Conclusion: </strong>This study highlights the potential role of AHCY in psoriasis development through its influence on DNA methylation. The findings underscore the complex interaction among AHCY, epigenetic modifications, and inflammation in the pathogenesis of psoriasis. Consequently, AHCY may serve as a promising therapeutic target for psoriasis treatment.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":"100-110"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}