{"title":"A20 ameliorates advanced glycation end products-induced melanogenesis by inhibiting NLRP3 inflammasome activation in human dermal fibroblasts","authors":"Mengyao Wang , Xianyin Huang , Mengting Ouyang , Jingjing Lan, Jingqian Huang, Hongpeng Li, Wei Lai, Yifeng Gao, Qingfang Xu","doi":"10.1016/j.jdermsci.2023.09.002","DOIUrl":"10.1016/j.jdermsci.2023.09.002","url":null,"abstract":"<div><h3>Background</h3><p>Advanced glycation end products (AGEs) promote melanogenesis through activating NLRP3 inflammasome in fibroblasts. Although A20 has been highlighted to inhibit NLRP3 inflammasome activation, its roles and mechanisms remain elusive in photoaging-associated pigmentation.</p></div><div><h3>Objectives</h3><p>To determine the significance of fibroblast A20 in AGEs-induced NLRP3 inflammasome activation and pigmentation.</p></div><div><h3>Methods</h3><p>The correlation between A20 and AGEs or melanin was studied in sun-exposed skin and lesions of melasma and solar lentigo. We then investigated A20 level in AGEs-treated fibroblast and the effect of fibroblast A20 overexpression or knockdown on AGEs-BSA-induced NLRP3 inflammasome activation and pigmentation, respectively. Finally, the severity of NLRP3 inflammasome activation and pigmentation was evaluated after mice were injected intradermally with A20-overexpression adeno-associated virus and AGEs-BSA.</p></div><div><h3>Results</h3><p>Dermal A20 expression was decreased and exhibited negative correlation with either dermal AGEs deposition or epidermal melanin level in sun-exposed skin and pigmentary lesions. Moreover, both AGEs-BSA and AGEs-collagen robustly decreased A20 expression via binding to RAGE in fibroblasts. Further, A20 overexpression or depletion significantly decreased or augmented AGEs-BSA-induced activation of NF-κB pathway and NLRP3 inflammasome and IL-18 production and secretion in fibroblasts, respectively. Importantly, fibroblast A20 potently repressed AGEs-BSA-stimulated melanin content,tyrosinase activity,and expression of microphthalmia-associated transcription factor and tyrosinase in melanocytes. Particularly, fibroblast A20 significantly abrogated AGEs-BSA-promoted melanogenesis in <em>ex vivo</em> skin and mouse models. Additionally, fibroblast A20 inhibited AGEs-BSA-activated MAPKs in melanocytes and the epidermis of <em>ex vivo</em> skin.</p></div><div><h3>Conclusions</h3><p>Fibroblast A20 suppresses AGEs-stimulate melanogenesis in photoaging-associated hyperpigmentation disorders by inhibiting NLRP3 inflammasome activation.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173262","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":"Molecular insights of human skin epidermal and dermal aging","authors":"Taihao Quan","doi":"10.1016/j.jdermsci.2023.08.006","DOIUrl":"10.1016/j.jdermsci.2023.08.006","url":null,"abstract":"<div><p>Human skin is the most widespread and abundant type of tissue in the human body. With the passage of time, most of our organs, including a substantial part of the skin, tend to undergo a gradual thinning or decrease in size. As we age, there is a gradual and progressive reduction in the thickness of both the epidermis and dermis<span><span> layers of our skin. This is primarily attributed to the decline of epidermal stem cells<span> and the loss of dermal collagen, which is the most abundant protein in the human body. Age-related alterations of the epidermis and dermis impair skin structure/function and create a tissue microenvironment that promotes age-related skin diseases, such as impaired skin barrier, </span></span>delayed wound healing, and skin cancer development. This review will examine the current body of literature pertaining to our knowledge of skin epidermal and dermal aging.</span></p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137286","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":"Transient receptor potential vanilloid 4 promotes cutaneous wound healing by regulating keratinocytes and fibroblasts migration and collagen production in fibroblasts in a mouse model","authors":"Bayarmaa Taivanbat , Sahori Yamazaki , Bolor Nasanbat , Akihiko Uchiyama , Syahla Nisaa Amalia , Munkhjargal Nasan-Ochir , Yuta Inoue , Mai Ishikawa , Keiji Kosaka , Akiko Sekiguchi , Sachiko Ogino , Yoko Yokoyama , Ryoko Torii , Mari Hosoi , Koji Shibasaki , Sei-ichiro Motegi","doi":"10.1016/j.jdermsci.2023.10.002","DOIUrl":"10.1016/j.jdermsci.2023.10.002","url":null,"abstract":"<div><h3>Background</h3><p>Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown.</p></div><div><h3>Objective</h3><p>To investigate the role of TRPV4 in cutaneous wound healing in a mouse model.</p></div><div><h3>Methods</h3><p>Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro.</p></div><div><h3>Results</h3><p><span>TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. </span><em>In vitro</em><span><span>, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in </span>keratinocytes, and TGF-β stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts.</span></p></div><div><h3>Conclusion</h3><p>TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242652","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":"Presence of microfibril associated glycoprotein 4 and type V collagen and the possible absence of fibrillin-1 in bead-like structures in elastofibroma","authors":"Haruto Nishida , Takako Sasaki , Yuki Taga , Yusuke Murasawa , Siro Simizu , Shigeto Matsushita , Zenzo Isogai , Shunji Hattori , Tsutomu Daa , Nobuo Nagamine , Akihiro Sekine , Sakuhei Fujiwara","doi":"10.1016/j.jdermsci.2023.09.005","DOIUrl":"10.1016/j.jdermsci.2023.09.005","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50164209","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}
Shilpa Kuttikrishnan , Tariq Masoodi , Fareed Ahmad , Gulab Sher , Kirti S. Prabhu , Jericha M. Mateo , Joerg Buddenkotte , Tamam El-Elimat , Nicholas H. Oberlies , Cedric J. Pearce , Ajaz A. Bhat , Feras Q. Alali , Martin Steinhoff , Shahab Uddin
{"title":"In vitro evaluation of Neosetophomone B inducing apoptosis in cutaneous T cell lymphoma by targeting the FOXM1 signaling pathway","authors":"Shilpa Kuttikrishnan , Tariq Masoodi , Fareed Ahmad , Gulab Sher , Kirti S. Prabhu , Jericha M. Mateo , Joerg Buddenkotte , Tamam El-Elimat , Nicholas H. Oberlies , Cedric J. Pearce , Ajaz A. Bhat , Feras Q. Alali , Martin Steinhoff , Shahab Uddin","doi":"10.1016/j.jdermsci.2023.10.001","DOIUrl":"10.1016/j.jdermsci.2023.10.001","url":null,"abstract":"<div><h3>Background</h3><p>Cutaneous T cell lymphoma<span> (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates.</span></p></div><div><h3>Objective</h3><p>In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH.</p></div><div><h3>Methods</h3><p><span><span>Cell viability was measured using Cell counting Kit-8 (CCK8) assays. </span>Apoptosis<span> was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human </span></span>Transcriptome Array 2.0 was used to examine gene expression.</p></div><div><h3>Results</h3><p><span><span>NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and </span>caspases<span>. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of </span></span>Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686677","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":"Invention of automated numerical algorithm adopting binarization for the evaluation of scalp hair coverage: An image analysis providing a substitute for phototrichogram and global photography assessment for hair diseases","authors":"Masaya Takagi , Misaki Kinoshita-Ise , Masahiro Fukuyama , Saori Nishikawa , Mami Miyoshi , Takaki Sugimoto , Masako Yamazaki , Masashi Ogo , Manabu Ohyama","doi":"10.1016/j.jdermsci.2023.09.003","DOIUrl":"10.1016/j.jdermsci.2023.09.003","url":null,"abstract":"<div><h3>Background</h3><p><span>The efficacy of therapeutic modalities for hair disease can be evaluated globally by photo assessment and more precisely by </span><u>p</u>hoto<u>t</u>richo<u>g</u>ram (PTG). However, the latter procedure is laborious, time consuming, subject to inter-observer variation, and requires hair clipping.</p></div><div><h3>Objective</h3><p>To establish an automated and patient/investigator friendly methodology enabling quantitative hair amount evaluation for daily clinical practice.</p></div><div><h3>Methods</h3><p>A novel <u>a</u>utomated <u>n</u>umerical <u>a</u><span>lgorithm (aNA) adopting digital image binarization (i.e., black and white color conversion) was invented to evaluate hair coverage and measure PTG parameters in scalp images. Step-by-step improvement of aNA was attempted through comparative analyses of the data obtained respectively by the novel approach and conventional PTG/</span><u>g</u>lobal <u>p</u>hotography <u>a</u>ssessment (GPA).</p></div><div><h3>Results</h3><p><span>For measuring scalp hair coverage, the initial version of aNA generally agreed with the cumulative hair diameter as assessed using PTG, showing a coefficient of 0.60. However, these outcomes were influenced by the angle of hair near the parting line. By integrating an angle compensation formula, the standard deviation of aNA data decreased from 5.7% to 1.2%. Consequently, the coefficient of determination for hair coverage calculated using the modified aNA and cumulative hair diameter assessed by PTG increased to 0.90. Furthermore, the change in hair coverage as determined by the modified aNA protocol correlated well with changes in the GPA score of images obtained using </span>clinical trials.</p></div><div><h3>Conclusion</h3><p>The novel aNA method provides a valuable tool for enabling simple and accurate evaluation of hair growth and volume for clinical trials and for treatment of hair disease.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41126188","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}
Janin Edelkamp , Marta B. Lousada , Daniela Pinto , Jérémy Chéret , Francesco Maria Calabrese , Francisco Jiménez , Hanieh Erdmann , Julia Wessel , Bodo Phillip , Maria De Angelis , Fabio Rinaldi , Marta Bertolini , Ralf Paus
{"title":"Management of the human hair follicle microbiome by a synthetic odorant","authors":"Janin Edelkamp , Marta B. Lousada , Daniela Pinto , Jérémy Chéret , Francesco Maria Calabrese , Francisco Jiménez , Hanieh Erdmann , Julia Wessel , Bodo Phillip , Maria De Angelis , Fabio Rinaldi , Marta Bertolini , Ralf Paus","doi":"10.1016/j.jdermsci.2023.09.006","DOIUrl":"10.1016/j.jdermsci.2023.09.006","url":null,"abstract":"<div><h3>Background</h3><p><span>Human scalp </span>hair follicles<span><span> (HFs) engage in olfactory receptor<span> (OR)-dependent chemosensation. Activation of olfactory receptor family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant Sandalore® up-regulated HF antimicrobial peptide expression of </span></span>dermcidin<span> (DCD), which had previously been thought to be produced exclusively by sweat and sebaceous glands.</span></span></p></div><div><h3>Objectives</h3><p>To understand if intrafollicular DCD production can be stimulated by a commonly used cosmetic odorant, thus altering human HF microbiome composition in a clinically beneficial manner.</p></div><div><h3>Methods</h3><p><span>DCD expression was compared between fresh-frozen scalp biopsies and microdissected, full-length scalp HFs, organ-cultured in the presence/absence of the OR2AT4 agonist, Sandalore® and/or antibiotics and/or the competitive OR2AT4 antagonist, Phenirat®. Amplicon-based sequencing and microbial growth assays were performed to assess how this </span>treatment affected the HF microbiome.</p></div><div><h3>Results</h3><p><span>Synthetic odorant treatment upregulated epithelial DCD expression and exerted antimicrobial activity in human HFs </span><span><em>ex vivo</em></span>. Combined antibiotic and odorant treatment, during an <em>ex vivo</em><span> dysbiosis event, prevented HF tissue damage and favoured a more physiological microbiome composition. Sandalore®-conditioned medium, containing higher DCD content, favoured </span><span><em>Staphylococcus epidermidis</em></span> and <span><em>Malassezia</em><em> restricta</em></span> over <span><em>S. aureus</em></span> and <em>M. globosa,</em> while exhibiting antimicrobial activity against <span><em>Cutibacterium acnes</em></span>. These effects were reversed by co-administration of Phenirat®.</p></div><div><h3>Conclusions</h3><p>We provide the first proof-of-principle that a cosmetic odorant impacts the human HF microbiome by up-regulating antimicrobial peptide production in an olfactory receptor-dependent manner. Specifically, a synthetic sandalwood-like odorant stimulates intrafollicular DCD production, likely via OR2AT4, and thereby controls microbial overgrowth. Thus, deserving further exploration as an adjuvant therapeutic principle in the management of folliculitis and dysbiosis-associated hair diseases.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686678","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 “A new susceptibility index to predict the risk of severe herpes zoster-associated pain: A Japanese regional population-based cohort study, the Shizuoka study” [J. Dermatol. Sci. 105 (2022) 170–175]","authors":"Hideo Hashizume , Eiji Nakatani , Yoko Sato , Haruka Goto , Hiroaki Yagi , Yoshiki Miyachi","doi":"10.1016/j.jdermsci.2023.11.001","DOIUrl":"10.1016/j.jdermsci.2023.11.001","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002396/pdfft?md5=669b3899b9dedff21727d01492f2596c&pid=1-s2.0-S0923181123002396-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721333","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}