Journal of dermatological science最新文献

{"title":"High α-diversity of skin microbiome and mycobiome in Japanese patients with vitiligo","authors":"Yasutaka Kuroda ,&nbsp;Lingli Yang ,&nbsp;Takakazu Shibata ,&nbsp;Masahiro Hayashi ,&nbsp;Yuta Araki ,&nbsp;Makiko Nishida ,&nbsp;Takeshi Namiki ,&nbsp;Teruhiko Makino ,&nbsp;Tadamichi Shimizu ,&nbsp;Tamio Suzuki ,&nbsp;Tetsuya Sayo ,&nbsp;Yoshito Takahashi ,&nbsp;Daisuke Tsuruta ,&nbsp;Ichiro Katayama","doi":"10.1016/j.jdermsci.2024.02.008","DOIUrl":"10.1016/j.jdermsci.2024.02.008","url":null,"abstract":"<div><h3>Background</h3><p>Vitiligo is an acquired pigmentary disorder characterized by depigmented patches on the skin that majorly impact patients' quality of life. Although its etiology involves genetic and environmental factors, the role of microorganisms as environmental factors in vitiligo pathology remains under-researched.</p></div><div><h3>Objectives</h3><p>Our study explored the presence of characteristic bacterial and fungal flora in vitiligo-affected skin and investigated their potential roles in vitiligo pathogenesis.</p></div><div><h3>Methods</h3><p>We sequenced bacterial 16S rRNA and the fungal ITS1 region from skin swabs collected at frequently affected sites, namely the forehead and back, of patients with vitiligo. We analyzed bacterial and fungal flora in lesional and non-lesional areas of patients with vitiligo compared with corresponding sites in age- and sex-matched healthy subjects.</p></div><div><h3>Results</h3><p>Our findings revealed elevated α-diversity in both bacterial and fungal flora within vitiligo lesions compared with healthy controls. Notably, bacterial flora exhibited a distinctive composition in patients with vitiligo, and the proportional representation of <em>Enterococcus</em> was inversely correlated with the degree of vitiligo progression. <em>Gammaproteobacteria</em>, <em>Staphylococcus</em> spp., and <em>Corynebacterium</em> spp. were more abundant in vitiligo patients, with notable <em>Staphylococcus</em> spp. prevalence during the stable phase on the forehead. Conversely, the proportion of <em>Malassezia sympodialis</em> was lower and that of <em>Malassezia globosa</em> was higher in the progressive phase on the back of vitiligo patients.</p></div><div><h3>Conclusion</h3><p>Our study identified some characteristic bacterial and fungal groups associated with vitiligo activity and prognosis, highlighting the potential roles of microorganisms in pathogenesis and offering insights into personalized disease-management approaches.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 1","pages":"Pages 34-43"},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000318/pdfft?md5=796a10391639e1c6cd440f6510cbb5c4&pid=1-s2.0-S0923181124000318-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178327","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":"Calcitriol modulates epidermal tight junction barrier function in human keratinocytes","authors":"Juan Valentin Trujillo-Paez ,&nbsp;Ge Peng ,&nbsp;Hai Le Thanh Nguyen ,&nbsp;Masahiro Nakamura ,&nbsp;Yoshie Umehara ,&nbsp;Hainan Yue ,&nbsp;Risa Ikutama ,&nbsp;Miho Takahashi ,&nbsp;Shigaku Ikeda ,&nbsp;Hideoki Ogawa ,&nbsp;Ko Okumura ,&nbsp;François Niyonsaba","doi":"10.1016/j.jdermsci.2024.02.001","DOIUrl":"10.1016/j.jdermsci.2024.02.001","url":null,"abstract":"<div><h3>Background</h3><p>The aberrant expression of tight junction (TJ) proteins play an important role in several diseases with impaired skin barriers, including atopic dermatitis, psoriasis, and chronic wounds. The evidence provided thus far suggests an important role of calcitriol in skin homeostasis. However, it is not known whether calcitriol improves the impaired skin barrier.</p></div><div><h3>Objective</h3><p>To investigate the effect of calcitriol on TJ barrier function in human primary keratinocytes.</p></div><div><h3>Methods</h3><p>Normal human primary keratinocytes were stimulated with calcitriol, and the expression of TJ-related proteins was measured by real-time PCR and Western blotting. Immunofluorescence was used to examine the intercellular distribution of TJ-related proteins. TJ barrier function was assessed by the transepithelial electrical resistance (TER) assay.</p></div><div><h3>Results</h3><p>We demonstrated that calcitriol increased the expression levels of TJ-related proteins, including claudin-4, claudin-7, occludin, and <em>zonula occludens</em> (ZO)− 1. Calcitriol enhanced the distribution of TJ-related proteins at cell<img>cell borders and induced the phosphorylation of pathways involved in the regulation of TJ barrier function, such as atypical protein kinase C (aPKC), Ras-related C3 botulinum toxin substrate 1 (Rac1), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt), as evidenced by the effects of specific inhibitors on the above pathways. Indeed, we confirmed that calcitriol enhanced TER in keratinocyte monolayers.</p></div><div><h3>Conclusion</h3><p>These findings showed that calcitriol could modify the expression of keratinocyte TJ proteins, contributing to the maintenance of homeostatic barrier function.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 1","pages":"Pages 13-23"},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139830104","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":"Targeting antibody-mediated complement-independent mechanism in bullous pemphigoid with diacerein","authors":"Yung-Tsu Cho ,&nbsp;Chih-Hung Lee ,&nbsp;Jing-Yi Lee ,&nbsp;Chia-Yu Chu","doi":"10.1016/j.jdermsci.2024.03.001","DOIUrl":"10.1016/j.jdermsci.2024.03.001","url":null,"abstract":"<div><h3>Background</h3><p>Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments.</p></div><div><h3>Objective</h3><p>We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein.</p></div><div><h3>Methods</h3><p>Cultured HaCaT cells were treated with purified antibodies from BP patients, with or without diacerein to measure the cell interface presence of BP180, protein kinase C, and the production of proinflammatory cytokines. An open-label, randomized, phase 2 trial was conducted to compare topical diacerein and clobetasol ointments in patients with mild-to-moderate BP (NCT03286582).</p></div><div><h3>Results</h3><p>The reduced presentation of BP180 at cell interface after treating with BP autoantibodies was noticed in immunofluorescence and western blotting studies. The phenomenon was restored by diacerein. Diacerein also reduced the autoantibody-induced increase of pro-inflammatory cytokines. Reciprocal changes of BP180 and protein kinase C at the cell interface were found after treating with BP autoantibodies. This phenomenon was also reversed by diacerein in a dose-dependent manner. The phase 2 trial showed that topical diacerein reduced the clinical symptoms which were comparable to those of topical clobetasol.</p></div><div><h3>Conclusion</h3><p>Diacerein inhibited BP autoantibody-induced reduction of BP180 and production of proinflammatory cytokines in vitro and showed therapeutic potential in patients with BP. It is a novel drug worthy of further investigations.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 1","pages":"Pages 44-51"},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140074574","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":"Proteomic changes related to actin cytoskeleton function in the skin of vildagliptin-treated mice","authors":"Antti Nätynki ,&nbsp;Nina Kokkonen ,&nbsp;Jussi Tuusa ,&nbsp;Steffen Ohlmeier ,&nbsp;Ulrich Bergmann ,&nbsp;Kaisa Tasanen","doi":"10.1016/j.jdermsci.2024.01.003","DOIUrl":"10.1016/j.jdermsci.2024.01.003","url":null,"abstract":"<div><h3>Background</h3><p>Vildagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i) is a widely used type 2 diabetes medication that is associated with an up-to 10-fold increased risk for the development of bullous pemphigoid (BP), an autoimmune skin disease. The mechanism by which vildagliptin promotes the development of BP remains unknown.</p></div><div><h3>Objective</h3><p>To elucidate effects of vildagliptin treatment on the mouse cutaneous proteome.</p></div><div><h3>Methods</h3><p>We analyzed the cutaneous proteome of nondiabetic mice treated for 12 weeks with vildagliptin using label-free shotgun mass spectrometry (MS), two-dimensional difference gel electrophoresis (2D-DIGE), immunohistochemistry, immunoblotting, and quantitative real-time polymerase chain reaction.</p></div><div><h3>Results</h3><p>Although vildagliptin treatment did not cause any clinical signs or histological changes in the skin, separate MS and 2D-DIGE analyses revealed altered cutaneous expression of several proteins, many of which were related to actin cytoskeleton remodeling. Altogether 18 proteins were increased and 40 were decreased in the vildagliptin-treated mouse skin. Both methods revealed increased levels of beta-actin and C-&gt;U-editing enzyme APOBEC2 in vildagliptin-treated mice. However, elevated levels of a specific moesin variant in vildagliptin-treated animals were only detected with 2D-DIGE. Immunohistochemical staining showed altered cutaneous expression of DPP-4, moesin, and galectin-1. The changed proteins detected by MS and 2D-DIGE were linked to actin cytoskeleton remodeling, transport, cell movement and organelle assembly.</p></div><div><h3>Conclusion</h3><p>Vildagliptin treatment alters the cutaneous proteome of nondiabetic mice even without clinical signs in the skin. Cytoskeletal changes in the presence of other triggering factors may provoke a break of immune tolerance and further promote the development of BP.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"113 3","pages":"Pages 121-129"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000112/pdfft?md5=fa59a26f8ead77c260c8005b8659af5f&pid=1-s2.0-S0923181124000112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139515231","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":"Editor's Choice","authors":"","doi":"10.1016/S0923-1811(24)00044-6","DOIUrl":"https://doi.org/10.1016/S0923-1811(24)00044-6","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"113 3","pages":"Page 85"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000446/pdfft?md5=b701227dd1c6ce7af31e062082e5aa5a&pid=1-s2.0-S0923181124000446-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140543685","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":"Acquired curved hair is caused by fusion of multiple hair matrix cells","authors":"Ippei Horibe ,&nbsp;Sara Izumi ,&nbsp;Yuru Ke ,&nbsp;Nanami Tanahashi ,&nbsp;Yusuke Takagi ,&nbsp;Ryoji Ishihara ,&nbsp;Takaya Nakano ,&nbsp;Takaaki Sumiyoshi ,&nbsp;Yasuo Nagaoka","doi":"10.1016/j.jdermsci.2024.02.002","DOIUrl":"10.1016/j.jdermsci.2024.02.002","url":null,"abstract":"<div><h3>Background</h3><p>“Curved hair” caused by acquired factors is considered to have adverse cosmetic effects, but the detailed mechanism behind curved hair remains obscure.</p></div><div><h3>Objective</h3><p>We attempted to clarify the causes of curved hair that appeared to have occurred via acquired factors.</p></div><div><h3>Methods</h3><p>Outer root sheath cells (ORSC) isolated from plucked human hair follicles were used to evaluate the expression of type IV collagen. Straight and curved hairs with hair follicle tissue attached were also collected from the same individuals and subjected to morphological, immunohistochemical, and gene expression analyses.</p></div><div><h3>Results</h3><p>The amount of type IV collagen increased upon inducing endoplasmic reticulum stress in ORSC. Meanwhile, in curved hair follicle tissue, the gene expression of type IV collagen decreased. In addition, the curved hair follicle tissue obtained from participants in their 30 s to 50 s had distorted shapes compared with that of straight hair from the same individuals. It was also observed that hair matrix cells based on multiple hair germs fused to eventually form a single hair follicle and hair shaft. In curved hair follicle tissue, KRT71 protein, a marker of inner root sheath differentiation, was unevenly distributed and there was elevated expression of Dickkopf-1 (DKK1) protein, an inhibitor of the Wnt signaling pathway.</p></div><div><h3>Conclusion</h3><p>Our study revealed the fusion of hair matrix cells during hair follicle regeneration as a cause of acquired curved hair. We consider that such fusion causes hair follicle tissue to abnormally differentiate, resulting in asymmetric hair follicle shapes and curved hair.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"113 3","pages":"Pages 130-137"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139827548","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":"Combined effect of Neurotropin® and methylcobalamin on postherpetic neuralgia in mice infected with herpes simplex virus type-1","authors":"Tsugunobu Andoh ,&nbsp;Takashi Kikukawa ,&nbsp;Atsushi Kotani ,&nbsp;Yoko Kurokawa ,&nbsp;Wakana Asakura ,&nbsp;Kengo Houmoto ,&nbsp;Daisuke Fukutomi ,&nbsp;Daisuke Uta ,&nbsp;Hisashi Okai ,&nbsp;Koji Koike","doi":"10.1016/j.jdermsci.2024.02.004","DOIUrl":"10.1016/j.jdermsci.2024.02.004","url":null,"abstract":"<div><h3>Background</h3><p>Postherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood.</p></div><div><h3>Objective</h3><p>In this study, we investigate the combined effects of NTP and MCB on PHP in mice.</p></div><div><h3>Methods</h3><p>NTP and MCB were administered from day 10–29 after herpes simplex virus type-1 (HSV-1) infection. The pain-related responses were evaluated using a paint brush. The expression of neuropathy-related factor (ATF3) and nerve repair factors (GAP-43 and SPRR1A) in the dorsal root ganglion (DRG) and neurons in the skin were evaluated by immunohistochemical staining. Nerve growth factor (NGF) and neurotrophin-3 (NT3) mRNA expression levels were evaluated using real-time PCR.</p></div><div><h3>Results</h3><p>Repeated treatment with NTP and MCB after the acute phase inhibited PHP. Combined treatment with these drugs inhibited PHP at an earlier stage than either treatment alone. In the DRG of HSV-1-infected mice, MCB, but not NTP, decreased the number of cells expressing ATF3 and increased the number of cells expressing GAP-43- and SPRR1A. In addition, MCB, but not NTP, also increased and recovered non-myelinated neurons decreased in the lesional skin. NTP increased the mRNA levels of NTF3 in keratinocytes, while MCB increased that of NGF in Schwann cells.</p></div><div><h3>Conclusion</h3><p>These results suggest that combined treatment with NTP and MCB is useful for the treatment of PHP. The combined effect may be attributed to the different analgesic mechanisms of these drugs.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"113 3","pages":"Pages 138-147"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139886023","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 GRHL3-regulated long non-coding RNA lnc-DC modulates keratinocytes differentiation by interacting with IGF2BP2 and up-regulating ZNF750","authors":"Xue-ting Hu ,&nbsp;Xiao-feng Wu ,&nbsp;Lu-min Sui ,&nbsp;Luo-quan Ao ,&nbsp;Cheng-xiu Pu ,&nbsp;Mu Yuan ,&nbsp;Wei Xing ,&nbsp;Xiang Xu","doi":"10.1016/j.jdermsci.2024.02.003","DOIUrl":"10.1016/j.jdermsci.2024.02.003","url":null,"abstract":"<div><h3>Background</h3><p>Aberrant keratinocytes differentiation has been demonstrated to be associated with a number of skin diseases. The roles of lncRNAs in keratinocytes differentiation remain to be largely unknown.</p></div><div><h3>Objective</h3><p>Here we aim to investigate the role of lnc-DC in regulating epidermal keratinocytes differentiation.</p></div><div><h3>Methods</h3><p>Expression of lnc-DC in the skin was queried in AnnoLnc and verified by FISH. The lncRNA expression profiles during keratinocytes differentiation were reanalyzed and verified by qPCR and FISH. Gene knock-down and over-expression were used to explore the role of lnc-DC in keratinocytes differentiation. The downstream target of lnc-DC was screened by whole transcriptome sequencing. CUT&amp;RUN assay and siRNAs transfection was used to reveal the regulatory effect of GRHL3 on lnc-DC. The mechanism of lnc-DC regulating ZNF750 was revealed by RIP assay and RNA stability assay.</p></div><div><h3>Results</h3><p>Lnc-DC was biasedly expressed in skin and up-regulated during epidermal keratinocytes differentiation. Knockdown lnc-DC repressed epidermal keratinocytes differentiation while over-express lnc-DC showed the opposite effect. GRHL3, a well-known transcription factor regulating keratinocytes differentiation, could bind to the promoter of lnc-DC and regulate its expression. By whole transcriptome sequencing, we identified that ZNF750 was a downstream target of lnc-DC during keratinocytes differentiation. Mechanistically, lnc-DC interacted with RNA binding protein IGF2BP2 to stabilize ZNF750 mRNA and up- regulated its downstream targets TINCR and KLF4.</p></div><div><h3>Conclusion</h3><p>Our study revealed the novel role of GRHL3/lnc-DC/ZNF750 axis in regulating epidermal keratinocytes differentiation, which may provide new therapeutic targets of aberrant keratinocytes differentiation related skin diseases.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"113 3","pages":"Pages 93-102"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139887385","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":"JAK inhibitors for the treatment of vitiligo","authors":"Shintaro Inoue ,&nbsp;Tamio Suzuki ,&nbsp;Shigetoshi Sano ,&nbsp;Ichiro Katayama","doi":"10.1016/j.jdermsci.2023.12.008","DOIUrl":"10.1016/j.jdermsci.2023.12.008","url":null,"abstract":"<div><p>Vitiligo<span><span> is an autoimmune disease involving melanocyte-targeting T cells initiated by environmental and </span>genetic factors<span><span><span><span>. Steroids and tacrolimus have been used as topical treatments. Recently, novel </span>topical agents<span> targeting Janus kinase (JAK), a family of </span></span>tyrosine kinases<span><span> that regulates cytokine signaling, have emerged. </span>Ruxolitinib<span> is the first approved in vitiligo therapy. Furthermore, ritlecitinib is currently under </span></span></span>clinical trials<span> for oral treatment of active vitiligo. In this review, we discuss the possibility of topical JAK inhibitors as promising options for the treatment of vitiligo with regard to their mechanism of action, efficacy and safety.</span></span></span></p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"113 3","pages":"Pages 86-92"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421452","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":"Decreased TET2/5-hmC reduces the integrity of the epidermal barrier via epigenetic dysregulation of filaggrin in psoriatic lesions","authors":"Huan Zhang ,&nbsp;Tao Jia ,&nbsp;Delu Che ,&nbsp;Bin Peng ,&nbsp;Zhaowei Chu ,&nbsp;Xiangjin Song ,&nbsp;Weihui Zeng ,&nbsp;Songmei Geng","doi":"10.1016/j.jdermsci.2024.01.004","DOIUrl":"10.1016/j.jdermsci.2024.01.004","url":null,"abstract":"<div><h3>Background</h3><p><span>TET2 participates in tumor progression and intrinsic immune homeostasis via </span>epigenetic<span> regulation. TET2 has been reported to be involved in maintaining epithelial barrier homeostasis and inflammation. Abnormal epidermal barrier function and TET2 expression have been detected in psoriatic lesions. However, the mechanisms underlying the role of TET2 in psoriasis have not yet been elucidated.</span></p></div><div><h3>Objective</h3><p>To define the role of TET2 in maintaining epithelial barrier homeostasis and the exact epigenetic mechanism in the dysfunction of the epidermal barrier in psoriasis.</p></div><div><h3>Methods</h3><p><span><span><span>We analyzed human psoriatic skin lesions and datasets from the </span>GEO database, and detected the expression of TET2/5-hmC together with barrier molecules by </span>immunohistochemistry<span>. We constructed epidermal-specific TET2 knockout mice to observe the effect of TET2 deficiency on epidermal barrier function via toluidine blue penetration assay. Further, we analyzed changes in the expression of epidermal barrier molecules by </span></span>immunofluorescence in TET2-specific knockout mice and psoriatic model mice.</p></div><div><h3>Results</h3><p><span><span><span>We found that decreased expression of TET2/5-hmC correlated with dysregulated barrier molecules in human psoriatic lesions. Epidermal-specific TET2 knockout mice showed elevated transdermal </span>water loss associated with abnormal epidermal barrier molecules. Furthermore, we observed that TET2 knockdown in </span>keratinocytes reduced </span>filaggrin<span> expression via filaggrin promoter methylation.</span></p></div><div><h3>Conclusion</h3><p>Aberrant epidermal TET2 affects the integrity of the epidermal barrier through the epigenetic dysregulation of epidermal barrier molecules, particularly filaggrin. Reduced TET2 expression is a critical factor contributing to an abnormal epidermal barrier in psoriasis.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"113 3","pages":"Pages 103-112"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514955","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}