Journal of dermatological science最新文献

{"title":"Mechanical stiffness promotes skin fibrosis through FAPα-AKT signaling pathway","authors":"Jiahao He ,&nbsp;Bin Fang ,&nbsp;Shengzhou Shan ,&nbsp;Qingfeng Li","doi":"10.1016/j.jdermsci.2023.12.004","DOIUrl":"10.1016/j.jdermsci.2023.12.004","url":null,"abstract":"<div><h3>Background</h3><p>Myofibroblasts contribute to the excessive production, remodeling and cross-linking of the extracellular matrix that characterizes the progression of skin fibrosis. An important insight into the pathogenesis of tissue fibrosis has been the discovery that increased matrix stiffness during fibrosis progression is involved in myofibroblast activation. However, mechanistic basis for this phenomenon remains elusive.</p></div><div><h3>Objective</h3><p>To explore the role of fibroblast activation protein-α (FAPα) in mechanical stiffness-induced skin fibrosis progression.</p></div><div><h3>Methods</h3><p>RNA-seq was performed to compare differential genes of mouse dermal fibroblasts (MDFs) grown on low or high stiffness plates. This process identified FAPα, which is a membrane protein usually overexpressed in activated fibroblasts, as a suitable candidate. In vitro assay, we investigate the role of FAPα in mechanical stiffness-induced MDFs activation and downstream pathway. By establishing mouse skin fibrosis model and intradermally administrating FAPα adeno-associated virus (AAV) or a selective Fap inhibitor FAPi, we explore the role of FAPα in skin fibrosis in vivo.</p></div><div><h3>Results</h3><p>We show that FAPα, a membrane protein highly expressed in myofibroblasts of skin fibrotic tissues, is regulated by increased matrix stiffness. Genetic deletion or pharmacological inhibition of FAPα significantly inhibits mechanical stiffness-induced activation of myofibroblasts in vitro. Mechanistically, FAPα promotes myofibroblast activation by stimulating the PI3K-Akt pathway. Furthermore, we showed that administration of the inhibitor FAPi or FAPα targeted knockdown ameliorated the progression of skin fibrosis.</p></div><div><h3>Conclusion</h3><p>Taken together, we identify FAPα as an important driver of mechanical stiffness-induced skin fibrosis and a potential therapeutic target for the treatment of skin fibrosis.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002542/pdfft?md5=ce756c068e8605126f19eac491729ed7&pid=1-s2.0-S0923181123002542-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138569297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resident memory T cell contributes to the phenotype of inflammatory vitiligo","authors":"Ken Okamura ,&nbsp;Takanobu Kabasawa ,&nbsp;Toru Saito ,&nbsp;Yosuke Arai ,&nbsp;Mitsuru Futakuchi ,&nbsp;Tamio Suzuki","doi":"10.1016/j.jdermsci.2024.01.002","DOIUrl":"10.1016/j.jdermsci.2024.01.002","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514942","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":"Exosomes containing miR-1469 regulate natural killer cells by targeting CD122 in non-segmental vitiligo","authors":"Yujia Wei ,&nbsp;Ting Zhou ,&nbsp;Ronghua Pan ,&nbsp;Xiaoqi Nie ,&nbsp;Zhong Liu ,&nbsp;Zeqi Shi ,&nbsp;Ying Zeng ,&nbsp;Ri Zhang ,&nbsp;Yunhua Deng ,&nbsp;Dong Li","doi":"10.1016/j.jdermsci.2023.12.006","DOIUrl":"10.1016/j.jdermsci.2023.12.006","url":null,"abstract":"<div><h3>Background</h3><p>Plasma exosomal microRNAs (miRNAs) have been used as potential biomarkers for various diseases and have been investigated for their possible involvement in the pathogenesis of vitiligo. However, the miRNA expression profile of plasma exosomes in patients with non-segmental vitiligo (NSV) has not been determined yet.</p></div><div><h3>Objective</h3><p>To screen differentially expressed microRNAs in plasma exosomes derived from patients with NSV and explore their roles in the pathogenesis of NSV.</p></div><div><h3>Methods</h3><p>High-throughput sequencing was performed to determine the expression profiles of exosomal miRNAs in NSV. The effect of upregulated miR-1469 in NSV circulating exosomes on natural killer (NK) cells was further investigated using various molecular biological techniques.</p></div><div><h3>Results</h3><p>MiR-1469 was identified as a candidate biomarker whose expression was significantly increased in circulating exosomes of NSV patients. Circulating exosomes were internalized by NK cells and increased NK cell proliferation viability and IFN-γ secretion capacity delivering miR-1469. Further studies revealed that the upregulation of CD122, the predicted target of miR-1469, could partially reverse the effect of miR-1469 on natural killer cells.</p></div><div><h3>Conclusion</h3><p>Alterations in plasma exosomal cargo occur in NSV and appear to contribute to NK cell dysfunction. Exosomal miR-1469 may be a biomarker of disease activity and could be used as a therapeutic drug target against innate immunity in NSV patients. The present study provides new insights into the role of exosomal miRNAs in NSV and suggests a novel miR-1469-CD122-IFN-γ pathway of NK cell underlying pathogenesis of NSV.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002694/pdfft?md5=c86839534ae89b96da0de299521d40a2&pid=1-s2.0-S0923181123002694-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139069996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome network analysis of inflammation and fibrosis in keloids","authors":"Jiayi Mao ,&nbsp;Lu Chen ,&nbsp;Shutong Qian ,&nbsp;Yuhuan Wang ,&nbsp;Binfan Zhao ,&nbsp;Qiuyu Zhao ,&nbsp;Bolun Lu ,&nbsp;Xiyuan Mao ,&nbsp;Peisong Zhai ,&nbsp;Yuguang Zhang ,&nbsp;Liucheng Zhang ,&nbsp;Xiaoming Sun","doi":"10.1016/j.jdermsci.2023.12.007","DOIUrl":"10.1016/j.jdermsci.2023.12.007","url":null,"abstract":"<div><h3>Background</h3><p>Keloid<span> (KL) is a common benign skin tumor. KL is typically characterized by significant fibrosis and an intensive inflammatory response. Therefore, a comprehensive understanding of the interactions between cellular inflammation and fibrotic cells is essential to elucidate the mechanisms driving the progression of KL and to develop therapeutics.</span></p></div><div><h3>Objective</h3><p>Investigate the transcriptome landscape of inflammation and fibrosis in keloid scars.</p></div><div><h3>Methods</h3><p><span>In this paper, we performed transcriptome sequencing and microRNA (miRNA) sequencing on unselected live cells from six human keloid tissues and normal skin tissues to elucidate a comprehensive transcriptome landscape. In addition, we used single-cell </span>RNA sequencing (scRNA-seq) analysis to analyze intercellular communication networks and enrich fibroblast populations in two additional keloid and normal skin samples to study fibroblast diversity.</p></div><div><h3>Results</h3><p>By RNA sequencing and a miRNA-mRNA-PPI network analysis, we identified miR-615–5p and miR-122b-3p as possible miRNAs associated with keloids, as they differed most significantly in keloids. Similarly, COL3A1, COL1A2, THBS2, TNC, IGTA, THBS4, TGFB3 as genes with significant differences in keloid may be associated with keloid development. Using single-cell RNA sequencing data from 24,086 cells collected from normal or keloid, we report reconstructed intercellular signaling network analysis and aggregation to modules associated with specific cell subpopulations at the cellular level for keloid alterations.</p></div><div><h3>Conclusions</h3><p>Our multitranscriptomic dataset delineates inflammatory and fibro heterogeneity of human keloids, underlining the importance of intercellular crosstalk between inflammatory cells and fibro cells and revealing potential therapeutic targets.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139069654","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 novel adiponectin receptor agonist APN5N alleviates sensitive skin by upregulating adiponectin expression","authors":"Eun Ju Kim ,&nbsp;Qing-Ling Quan ,&nbsp;Soo Ick Cho ,&nbsp;Yeon Kyung Kim ,&nbsp;Dong Hun Lee ,&nbsp;Jin Ho Chung","doi":"10.1016/j.jdermsci.2023.12.002","DOIUrl":"10.1016/j.jdermsci.2023.12.002","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138569310","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":"Editor's Choice","authors":"","doi":"10.1016/S0923-1811(24)00024-0","DOIUrl":"https://doi.org/10.1016/S0923-1811(24)00024-0","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000240/pdfft?md5=757655e21620f56a35b7b5a00878c67f&pid=1-s2.0-S0923181124000240-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140042317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-sectional nationwide epidemiologic survey on quality of life and treatment efficacy in Japanese patients with congenital ichthyoses","authors":"Yuika Suzuki ,&nbsp;Kana Tanahashi ,&nbsp;Chiaki Terashima-Murase ,&nbsp;Takuya Takeichi ,&nbsp;Yumiko Kobayashi ,&nbsp;Fumie Kinoshita ,&nbsp;Masashi Akiyama","doi":"10.1016/j.jdermsci.2023.11.002","DOIUrl":"10.1016/j.jdermsci.2023.11.002","url":null,"abstract":"<div><h3>Background</h3><p>Congenital ichthyoses sometimes present with severe skin symptoms that significantly affect the patient’s quality of life (QOL). Symptomatic treatments are the mainstay therapies, and their efficacy is limited and inadequate.</p></div><div><h3>Objective</h3><p>To assess the disease severity and QOL in patients with congenital ichthyoses, and to investigate the effectiveness of current treatments.</p></div><div><h3>Methods</h3><p>We conducted a questionnaire-based Japan-wide epidemiological survey of patients with congenital ichthyosis who received medical care from 1 January 2016–31 December 2020. Effectiveness of past and current treatments was assessed. The outcomes were the physician’s assessment, disease severity assessed using the clinical ichthyosis score (CIS), and the disease burden estimated using the Dermatology Life Quality Index (DLQI), the Children’s Dermatology Life Quality Index (CDLQI), and the Infants’ Dermatitis Quality of Life Index.</p></div><div><h3>Results</h3><p>One hundred patients with 14 ichthyosis subtypes from 47 institutes were included in the final analysis. The CDLQI score showed a positive correlation with CIS (rs = 0.59, p = 0.004), while the DLQI score showed no significant correlation (rs = 0.13, p = 0.33). All existing medications were effective for many patients. Etretinate improved QOL and reduced CIS, but side effects including bone growth retardation were reported. Decreased treatment willingness was observed in patients with very low and very high CIS.</p></div><div><h3>Conclusion</h3><p>QOL scores were found to correlate with CIS in children, but not in adults. Considering the adverse events, it is speculated that etretinate is not indicated for children with mild cases. Petrolatum was the most commonly used medication, even in patients who were reluctant to receive treatment.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002402/pdfft?md5=5c7239bcc1b32fb181cfd14937c4981e&pid=1-s2.0-S0923181123002402-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EDA-A2 increases lipid production in EDA2R-expressing human sebocytes","authors":"Mi Hee Kwack,&nbsp;Ons Ben Hamida,&nbsp;Weon Ju Lee,&nbsp;Moon Kyu Kim","doi":"10.1016/j.jdermsci.2023.11.005","DOIUrl":"10.1016/j.jdermsci.2023.11.005","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002438/pdfft?md5=06e4e544c502757e0a662ab483ac694a&pid=1-s2.0-S0923181123002438-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of skin barrier abnormalities and epidermal ceramide profiles among three ω-O-acylceramide synthesis-deficient mouse strains","authors":"Yuta Yamamoto,&nbsp;Takayuki Sassa,&nbsp;Akio Kihara","doi":"10.1016/j.jdermsci.2023.12.003","DOIUrl":"10.1016/j.jdermsci.2023.12.003","url":null,"abstract":"<div><h3>Background</h3><p>The epidermis contains many structurally diverse ceramides, which form the skin permeability barrier (skin barrier). Mutations in genes involved in the synthesis of ω-<em>O</em>-acylceramides (acylceramides) and protein-bound ceramides cause ichthyosis.</p></div><div><h3>Objective</h3><p>We aimed to elucidate the relationship between the degree of skin barrier impairment and changes in epidermal ceramide profiles caused by mutations in acylceramide synthesis genes.</p></div><div><h3>Methods</h3><p>Knockout (KO) mice of three genes—fatty acid (FA) ω-hydroxylase <em>Cyp4f39</em> (human <em>CYP4F22</em> ortholog), FA elongase <em>Elovl1</em>, and acyl-CoA synthetase <em>Fatp4</em>—were subjected to transepidermal water loss measurement, toluidine blue staining, and epidermal ceramide profiling via liquid chromatography coupled with tandem mass spectrometry.</p></div><div><h3>Results</h3><p>Transepidermal water loss was highest in <em>Cyp4f39</em> KO mice, followed by <em>Elovl1</em> KO and <em>Fatp4</em> KO mice, and <em>Cyp4f39</em> KO mice also showed the strongest degree of toluidine blue staining. In <em>Cyp4f39</em> KO, <em>Elovl1</em> KO, and <em>Fatp4</em> KO mice, acylceramide levels were 0.6%, 1.6%, and 12%, respectively, of those in wild-type mice. Protein-bound ceramide levels were 0.2%, 30%, and 33%, respectively, of those in wild-type mice. We also observed a near-complete absence of ω-hydroxy ceramides in <em>Cyp4f39</em> KO mice, reduced total ceramide levels and shortened FA moieties in <em>Elovl1</em> KO mice, and increased hydroxylated ceramide levels and slightly shortened FA moieties in <em>Fatp4</em> KO mice.</p></div><div><h3>Conclusions</h3><p>The degree of reduction in protein-bound ceramide levels is probably related to the severity of skin barrier defects in these three strains. However, reduced acylceramide levels and other changes in ceramide composition unique to each KO strain are also involved.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002530/pdfft?md5=68738f63a9acc9d97398d25527c80898&pid=1-s2.0-S0923181123002530-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138569312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway","authors":"Zheng-Yi Li ,&nbsp;Shu-Hao Chang ,&nbsp;Kuang-Ting Liu ,&nbsp;Alaina Edelie Wu ,&nbsp;Chien-Sheng Hsu ,&nbsp;Shi-Wei Huang ,&nbsp;Mu-Chi Chung ,&nbsp;Shih-Chung Wang ,&nbsp;Jun-Kai Kao ,&nbsp;Yi-Ju Chen ,&nbsp;Jeng-Jer Shieh","doi":"10.1016/j.jdermsci.2023.12.005","DOIUrl":"10.1016/j.jdermsci.2023.12.005","url":null,"abstract":"<div><h3>Background</h3><p>Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity.</p></div><div><h3>Objective</h3><p>To explore whether IMQ could induce melanogenesis in melanoma cells.</p></div><div><h3>Methods</h3><p>The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not.</p></div><div><h3>Results</h3><p>We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity.</p></div><div><h3>Conclusions</h3><p>Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002682/pdfft?md5=e1076029cba3585ea1eb90f735db9d14&pid=1-s2.0-S0923181123002682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139020882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}