{"title":"High migratory activity of dermal sheath cup cells associated with the clinical efficacy of autologous cell-based therapy for pattern hair loss","authors":"Yumiko Ishimatsu-Tsuji , Shiro Niiyama , Ryokichi Irisawa , Kazutoshi Harada , Jiro Kishimoto , Ryoji Tsuboi","doi":"10.1016/j.jdermsci.2023.11.003","DOIUrl":"10.1016/j.jdermsci.2023.11.003","url":null,"abstract":"<div><h3>Background</h3><p>Autologous cell-based therapy using dermal sheath cup (DSC) cells was reported as a new treatment for male and female pattern hair loss. However, the mechanisms underlying its action remain unclear.</p></div><div><h3>Objective</h3><p>We investigated the mechanisms underlying the efficacy of DSC cells in cell-based therapy.</p></div><div><h3>Methods</h3><p>We conducted multivariate analysis to categorize individuals based on treatment response as responders and non-responders. The differentially expressed genes in DSC cells from the two groups were evaluated using bulk transcriptome, quantitative polymerase chain reaction, and single-cell transcriptome analyses. We performed live cell imaging combined with immunostaining to characterize the DSC subpopulation associated with responders.</p></div><div><h3>Results</h3><p>We identified nine and three genes as high efficacy (HE) and low efficacy (LE) marker genes, respectively. The HE subpopulations were enriched for cell migration-related genes in single-cell analysis. In contrast, the LE subpopulation was enriched for basement membrane and vasculature-related genes. Moreover, DSC cells in culture were immunocytochemically and morphologically heterogeneous, expressing characteristic factors. Furthermore, live cell imaging showed that DSC cells expressing integrin subunit alpha 6 (ITGA6), an HE subpopulation gene, had markedly higher mobility than those expressing the LE subpopulation genes collagen type IV or CD36.</p></div><div><h3>Conclusions</h3><p>ITGA6-positive DSC cells, with superior migratory activity, may contribute to cell-based therapy by promoting cell migration into nearby hair follicles.</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/S0923181123002414/pdfft?md5=edfa610e798cd3f1b2fb6eed9771d813&pid=1-s2.0-S0923181123002414-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135615370","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}
Yu Guo, Yongjie Wang, Haiwei Liu, Xulei Jiang, Shaorong Lei
{"title":"High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing","authors":"Yu Guo, Yongjie Wang, Haiwei Liu, Xulei Jiang, Shaorong Lei","doi":"10.1016/j.jdermsci.2023.09.007","DOIUrl":"10.1016/j.jdermsci.2023.09.007","url":null,"abstract":"<div><h3>Background</h3><p>Healing of diabetic wounds, characterized by impaired angiogenesis<span>, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing.</span></p></div><div><h3>Objective</h3><p>We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing.</p></div><div><h3>Methods</h3><p><span>The mRNA expression levels of NEDD4, TSP1<span><span> and VEGF were determined by real-time PCR. Western blotting was used to evaluate the </span>protein expression of NEDD4, TSP1 and VEGF. The </span></span>ubiquitination<span><span> of TSP1 was evaluated by immunoprecipitation. </span>MTT assay<span><span>, wound healing assay and tube formation assay were performed to assess the proliferation, migration and angiogenic functions of endothelial cells. The </span>epigenetic modification in the promoter of NEDD4 was confirmed using BSP assay and ChIP-qPCR assay. The role of NEDD4 in wound healing was further verified in diabetic mouse model.</span></span></p></div><div><h3>Results</h3><p>NEDD4 promotes proliferation, migration and tube formation of endothelial cells. It binds to and ubiquitinates TSP1, which lead to TSP1 degradation and thus increased VEGF expression. The inhibitory effect of NEDD4 silencing on the angiogenesis ability of endothelial cells can be restored by TSP1 knockdown. NEDD4 is reduced in diabetic patients, which may due to hypermethylation of NEDD4 promoter mediated via DNMT1 under high glucose condition. Furthermore, inhibition of NEDD4 represses wound healing in diabetic mouse model.</p></div><div><h3>Conclusion</h3><p>NEDD4 might promote angiogenesis and wound healing by inhibiting TSP1 via ubiquitination in diabetic patients.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490526","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":"Alopecia areata: What’s new in the epidemiology, comorbidities, and pathogenesis?","authors":"Teruki Dainichi , Masashi Iwata , Yo Kaku","doi":"10.1016/j.jdermsci.2023.09.008","DOIUrl":"10.1016/j.jdermsci.2023.09.008","url":null,"abstract":"<div><h3>Background</h3><p><span>Alopecia areata<span> (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases. Patients with AA, especially those with greater scalp involvement, have poor health-related quality-of-life scores. Purpose: Following our previous review article in the April 2017 issue of the Journal of Dermatological Science, we aim to provide a pair of review articles on recent progress in multidisciplinary approaches to AA. Main findings: We found more than 1800 publications on AA from July 2016 to December 2022. Conclusions: In this review, we focused on the latest information on the </span></span>epidemiology, comorbidities, and pathogenesis of AA.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224132","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}
Renpeng Zhou , Qirui Wang , Siyi Zeng, Yimin Liang, Danru Wang
{"title":"METTL14-mediated N6-methyladenosine modification of Col17a1/Itgα6/Itgβ4 governs epidermal homeostasis","authors":"Renpeng Zhou , Qirui Wang , Siyi Zeng, Yimin Liang, Danru Wang","doi":"10.1016/j.jdermsci.2023.10.005","DOIUrl":"10.1016/j.jdermsci.2023.10.005","url":null,"abstract":"<div><h3>Background</h3><p>N6-methyladenosine (m<sup>6</sup>A) is the most abundant and reversible modification occurring in eukaryotic mRNAs, however, its functions in mammalian epidermal development are still not fully elucidated.</p></div><div><h3>Objective</h3><p>To explore the role of METTL14 (Methyltransferase like 14), one of the m<sup>6</sup><span>A methyltransferases, in maintaining epidermal homeostasis.</span></p></div><div><h3>Methods</h3><p>We constructed mice with <em>Mettl14</em><span><span>-inactivation in the epidermal basal cells. The phenotype was explored by H&E staining and </span>immunofluorescence staining. To explore the underlying mechanisms, we performed RNA-seq, Ribosome profiling and MeRIP-seq on wild-type and </span><em>Mettl14</em><span><span>-inactivation epidermal keratinocytes. Moreover, </span>HaCaT cells were used for </span><em>in vitro</em> validation.</p></div><div><h3>Results</h3><p>Inactivation of <em>Mettl14</em><span><span><span> in murine epidermis led to transient thicker epidermis and exhaustion of the epidermal stem cell pool. Interestingly, we found that the mRNA of </span>type XVII collagen (Col17a1), </span>integrin β4 (Itgβ4) and α6 (Itgα6) had m</span><sup>6</sup><span>A modifications, and the proteins expression were decreased in </span><em>Mettl14</em>-inactivated epidermis. Furthermore, in epidermis-specific <em>Mettl4</em><span><span>-inactivated mice, the epidermis was detached from the dermis and presented a phenotype similar to </span>junctional epidermolysis bullosa<span> (JEB), which may result from hemidesmosomes damage (decrease of COL17A1, ITGB4 and ITGA6). Knockdown of </span></span><em>Mettl14</em> in HaCaT cells impaired the self-renewal and decreased the protein level of COL17A1, ITGB4 and ITGA6 and <em>Itgβ4</em> knockdown inhibited colony formation.</p></div><div><h3>Conclusion</h3><p>Our study highlighted the role of METTL14 in the maintenance of epidermal homeostasis and identified its critical role through m<sup>6</sup><span>A-mediated translational inhibition of Col17a1, Itgβ4 and Itgα6. Our study suggested that METTL14 may be a potential therapeutic target for the treatment of hemidesmosomes-deficient diseases, such as JEB.</span></p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721336","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}
Xueshan Du , Delu Che , Bin Peng , Yi Zheng , Yong Hao , Tao Jia , Xinyue Zhang , Songmei Geng
{"title":"Dual effect of tacrolimus on mast cell–mediated allergy and inflammation through Mas-related G protein-coupled receptor X2","authors":"Xueshan Du , Delu Che , Bin Peng , Yi Zheng , Yong Hao , Tao Jia , Xinyue Zhang , Songmei Geng","doi":"10.1016/j.jdermsci.2023.10.003","DOIUrl":"10.1016/j.jdermsci.2023.10.003","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Topical tacrolimus<span>, although widely used in the treatment of </span></span>dermatoses<span>, presents with an immediate irritation on initial application resembling a pseudo-allergic reaction. Mas-related G protein-coupled receptor X2 (MRGPRX2) in mast cells (MCs) mediates drug-induced pseudo-allergic reaction and immunoglobulin E (IgE)-independent pruritis in chronic skin diseases. However, the immunosuppression mechanism of tacrolimus on MCs </span></span><em>via</em> MRGPRX2 has not been reported.</p></div><div><h3>Objective</h3><p>To investigate the role of MRGPRX2 and the mechanism of action of tacrolimus on its short-term and long-term applications.</p></div><div><h3>Methods</h3><p>Wild-type mice, Kit<sup>W-sh/W-sh</sup> mice, and MrgprB2-deficient (MUT) mice were used to study the effect of tacrolimus on <em>in vivo</em> anaphylaxis model. LAD2 cells and MRGPRX2-knockdown LAD2 cells were specifically used to derive the associated mechanism of the tacrolimus effect.</p></div><div><h3>Results</h3><p>Short-term application of tacrolimus triggers IgE-independent activation of MCs <em>via</em> MRGPRX2/B2 in both <em>in vivo</em> and <em>in vitro</em><span> experiments. Tacrolimus binds to MRGPRX2, which was verified by fluorescently labeled tacrolimus in cells. On long-term treatment with tacrolimus, the initial allergic reaction fades away corresponding with the downregulation of MRGPRX2, which leads to decreased release of inflammatory cytokines (</span><em>P</em> < 0.05 to <em>P</em> < 0.001).</p></div><div><h3>Conclusion</h3><p>Short-term treatment with tacrolimus induces pseudo-allergic reaction <em>via</em><span> MRGPRX2/B2 in MCs, whereas long-term treatment downregulates expression of MRGPRX2/B2, which may contribute to its potent immunosuppressive effect in the treatment of various skin diseases.</span></p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721335","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}