Journal of dermatological science最新文献

英文中文

EDA-A2 increases lipid production in EDA2R-expressing human sebocytes EDA-A2增加表达eda2r的人脂质细胞的脂质生成。

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.11.005

Mi Hee Kwack, Ons Ben Hamida, Weon Ju Lee, Moon Kyu Kim

引用次数: 0

Comparison of skin barrier abnormalities and epidermal ceramide profiles among three ω-O-acylceramide synthesis-deficient mouse strains 比较三种ω-O-甘油酰胺合成缺陷小鼠品系的皮肤屏障异常和表皮神经酰胺特征

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.12.003

Yuta Yamamoto, Takayuki Sassa, Akio Kihara

Background

The epidermis contains many structurally diverse ceramides, which form the skin permeability barrier (skin barrier). Mutations in genes involved in the synthesis of ω-O-acylceramides (acylceramides) and protein-bound ceramides cause ichthyosis.

Objective

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.

Methods

Knockout (KO) mice of three genes—fatty acid (FA) ω-hydroxylase Cyp4f39 (human CYP4F22 ortholog), FA elongase Elovl1, and acyl-CoA synthetase Fatp4—were subjected to transepidermal water loss measurement, toluidine blue staining, and epidermal ceramide profiling via liquid chromatography coupled with tandem mass spectrometry.

Results

Transepidermal water loss was highest in Cyp4f39 KO mice, followed by Elovl1 KO and Fatp4 KO mice, and Cyp4f39 KO mice also showed the strongest degree of toluidine blue staining. In Cyp4f39 KO, Elovl1 KO, and Fatp4 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 Cyp4f39 KO mice, reduced total ceramide levels and shortened FA moieties in Elovl1 KO mice, and increased hydroxylated ceramide levels and slightly shortened FA moieties in Fatp4 KO mice.

Conclusions

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.

背景表皮中含有许多结构各异的神经酰胺，它们构成了皮肤的通透性屏障（皮肤屏障）。参与合成ω-O-酰基甘油酰胺（酰基甘油酰胺）和蛋白结合神经酰胺的基因发生突变会导致鱼鳞病。目的我们旨在阐明皮肤屏障受损程度与酰基甘油酰胺合成基因突变导致的表皮神经酰胺谱变化之间的关系。方法对脂肪酸（FA）ω-羟化酶 Cyp4f39（人类 CYP4F22 同源物）、FA 延长酶 Elovl1 和酰基-CoA 合成酶 Fatp4 这三个基因的基因敲除（KO）小鼠进行经表皮失水测量、甲苯胺蓝染色和液相色谱-串联质谱表皮神经酰胺谱分析。结果 Cyp4f39 KO小鼠的经表皮失水率最高，其次是Elovl1 KO和Fatp4 KO小鼠，Cyp4f39 KO小鼠的甲苯胺蓝染色程度也最强。在 Cyp4f39 KO、Elovl1 KO 和 Fatp4 KO 小鼠中，酰基神经酰胺水平分别是野生型小鼠的 0.6%、1.6% 和 12%。蛋白结合的神经酰胺水平分别为野生型小鼠的 0.2%、30% 和 33%。我们还观察到，在 Cyp4f39 KO 小鼠中，ω-羟基神经酰胺几乎完全缺失；在 Elovl1 KO 小鼠中，总神经酰胺水平降低，FA 分子缩短；在 Fatp4 KO 小鼠中，羟基化神经酰胺水平升高，FA 分子略有缩短。然而，酰基神经酰胺水平的降低和每个 KO 株系特有的神经酰胺组成的其他变化也与此有关。

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引用次数: 0

Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway 低剂量咪喹莫特通过 ROS 介导的途径诱导黑色素瘤细胞的黑色素生成

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.12.005

Zheng-Yi Li , Shu-Hao Chang , Kuang-Ting Liu , Alaina Edelie Wu , Chien-Sheng Hsu , Shi-Wei Huang , Mu-Chi Chung , Shih-Chung Wang , Jun-Kai Kao , Yi-Ju Chen , Jeng-Jer Shieh

Background

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.

Objective

To explore whether IMQ could induce melanogenesis in melanoma cells.

Methods

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.

Results

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.

Conclusions

Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

背景黑色素生成是黑色素成熟的过程，它不仅能保护皮肤免受紫外线辐射，还在黑色素瘤的抗原性方面发挥着重要作用。方法本研究利用小鼠黑色素瘤细胞系B16F10、小鼠永生黑色素细胞Melan-A以及人黑色素瘤细胞系MNT-1、C32和A375。色素水平通过离心后的细胞团进行观察。细胞内和细胞外黑色素水平分别通过 NaOH 提取的细胞裂解液和细胞培养培养基的吸光度进行检测。用免疫印迹法检测黑色素生成相关蛋白的表达。细胞内环磷酸腺苷的含量由 cAMP Glo 检测试剂盒进行评估。结果我们证明，低剂量的IMQ可诱导B16F10细胞的黑色素生成。IMQ诱导小眼球相关转录因子（MITF）核转位，上调黑色素生成相关蛋白的表达，增加酪氨酸酶（TYR）活性，导致B16F10细胞色素沉着。接着，我们发现 IMQ 诱导的黑色素生成是由细胞内过量的 cAMP 积累激活的，而这种积累是通过 IMQ 介导的 PDE4B 抑制来调节的。结论低剂量 IMQ 可通过黑色素瘤细胞中的 ROS/PDE4B/PKA 通路激活黑色素生成。

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引用次数: 0

A modified Sobel filter-based automated numerical algorithm enables immediate trichoscopic assessment of hair diameter diversity in male and female pattern hair loss 一种改进的基于索贝尔过滤器的自动数值算法，可以立即对男性和女性脱发的头发直径多样性进行三分镜评估。

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.11.004

Masaya Takagi, Misaki Kinoshita-Ise, Masahiro Fukuyama, Soichiro Aoki, Saori Nishikawa, Mami Miyoshi, Takaki Sugimoto, Masako Yamazaki, Masashi Ogo, Manabu Ohyama

引用次数: 0

Editor's Choice 编辑推荐

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/S0923-1811(24)00006-9

引用次数: 0

High migratory activity of dermal sheath cup cells associated with the clinical efficacy of autologous cell-based therapy for pattern hair loss 真皮鞘杯细胞的高迁移活性与自体细胞疗法治疗脱发的临床疗效有关

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.11.003

Yumiko Ishimatsu-Tsuji , Shiro Niiyama , Ryokichi Irisawa , Kazutoshi Harada , Jiro Kishimoto , Ryoji Tsuboi

Background

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.

Objective

We investigated the mechanisms underlying the efficacy of DSC cells in cell-based therapy.

Methods

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.

Results

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.

Conclusions

ITGA6-positive DSC cells, with superior migratory activity, may contribute to cell-based therapy by promoting cell migration into nearby hair follicles.

背景据报道，使用真皮鞘杯（DSC）细胞的自体细胞疗法是治疗男性和女性脱发的一种新疗法。方法我们进行了多变量分析，根据治疗反应将个体分为有反应者和无反应者。我们使用大量转录组、定量聚合酶链反应和单细胞转录组分析评估了两组 DSC 细胞中的差异表达基因。我们进行了活细胞成像并结合免疫染色，以确定与应答者相关的 DSC 亚群的特征。结果我们分别确定了 9 个和 3 个基因作为高效（HE）和低效（LE）标记基因。在单细胞分析中，HE 亚群富含细胞迁移相关基因。相比之下，LE 亚群富含基底膜和血管相关基因。此外，培养中的 DSC 细胞在免疫细胞化学和形态上具有异质性，表达特征性因子。此外，活细胞成像显示，表达整合素亚单位α6（ITGA6）（一种 HE 亚群基因）的 DSC 细胞比表达 LE 亚群基因Ⅳ型胶原蛋白或 CD36 的细胞具有明显更高的迁移性。

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引用次数: 0

High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing 高糖环境诱导NEDD4缺乏，从而损害血管生成和糖尿病伤口愈合。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.09.007

Yu Guo, Yongjie Wang, Haiwei Liu, Xulei Jiang, Shaorong Lei

Background

Healing of diabetic wounds, characterized by impaired angiogenesis, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing.

Objective

We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing.

Methods

The mRNA expression levels of NEDD4, TSP1 and VEGF were determined by real-time PCR. Western blotting was used to evaluate the protein expression of NEDD4, TSP1 and VEGF. The ubiquitination of TSP1 was evaluated by immunoprecipitation. MTT assay, wound healing assay and tube formation assay were performed to assess the proliferation, migration and angiogenic functions of endothelial cells. The 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.

Results

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.

Conclusion

NEDD4 might promote angiogenesis and wound healing by inhibiting TSP1 via ubiquitination in diabetic patients.

背景：以血管生成受损为特征的糖尿病伤口的愈合仍然是一个临床挑战。E3连接酶已被确定为伤口愈合的潜在治疗靶点。目的：我们评估了E3连接酶NEDD4在血管生成和糖尿病伤口愈合中的作用。方法：采用实时聚合酶链反应检测NEDD4、TSP1和VEGF的mRNA表达水平。采用蛋白质印迹法检测NEDD4、TSP1和VEGF的蛋白表达。TSP1的泛素化通过免疫沉淀进行评估。MTT法、创伤愈合法和成管法检测内皮细胞的增殖、迁移和血管生成功能。使用BSP分析和ChIP-qPCR分析证实了NEDD4启动子的表观遗传学修饰。在糖尿病小鼠模型中进一步验证了NEDD4在伤口愈合中的作用。结果：NEDD4能促进内皮细胞的增殖、迁移和管形成。它与TSP1结合并泛素化，从而导致TSP1降解，从而增加VEGF的表达。NEDD4沉默对内皮细胞血管生成能力的抑制作用可以通过敲低TSP1来恢复。糖尿病患者的NEDD4减少，这可能是由于在高糖条件下通过DNMT1介导的NEDD4-启动子的高甲基化。此外，在糖尿病小鼠模型中，NEDD4的抑制抑制伤口愈合。结论：NEDD4可能通过泛素化抑制TSP1，从而促进糖尿病患者血管生成和伤口愈合。

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引用次数: 0

Alopecia areata: What’s new in the epidemiology, comorbidities, and pathogenesis? 斑秃：流行病学、合并症和发病机制有什么新进展？

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.09.008

Teruki Dainichi , Masashi Iwata , Yo Kaku

Background

Alopecia areata (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 epidemiology, comorbidities, and pathogenesis of AA.

背景：斑秃（AA）是一种常见的、获得性的、非持续性的脱发，影响每一代人，在严重和复发的病例中很难治愈。AA患者，尤其是头皮受累较多的患者，健康相关生活质量评分较差。目的：继我们在《皮肤病学杂志》2017年4月号上发表的上一篇综述文章之后，我们的目标是提供两篇关于AA多学科方法最新进展的综述文章。主要发现：从2016年7月到2022年12月，我们发现了1800多篇关于AA的出版物。结论：在这篇综述中，我们重点关注流行病学的最新信息，合并症和AA的发病机制。

引用次数: 0

METTL14-mediated N6-methyladenosine modification of Col17a1/Itgα6/Itgβ4 governs epidermal homeostasis mettl14介导的Col17a1/Itgα6/Itgβ4的n6 -甲基腺苷修饰控制表皮稳态。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.10.005

Renpeng Zhou , Qirui Wang , Siyi Zeng, Yimin Liang, Danru Wang

Background

N6-methyladenosine (m⁶A) is the most abundant and reversible modification occurring in eukaryotic mRNAs, however, its functions in mammalian epidermal development are still not fully elucidated.

Objective

To explore the role of METTL14 (Methyltransferase like 14), one of the m⁶A methyltransferases, in maintaining epidermal homeostasis.

Methods

We constructed mice with Mettl14-inactivation in the epidermal basal cells. The phenotype was explored by H&E staining and immunofluorescence staining. To explore the underlying mechanisms, we performed RNA-seq, Ribosome profiling and MeRIP-seq on wild-type and Mettl14-inactivation epidermal keratinocytes. Moreover, HaCaT cells were used for in vitro validation.

Results

Inactivation of Mettl14 in murine epidermis led to transient thicker epidermis and exhaustion of the epidermal stem cell pool. Interestingly, we found that the mRNA of type XVII collagen (Col17a1), integrin β4 (Itgβ4) and α6 (Itgα6) had m⁶A modifications, and the proteins expression were decreased in Mettl14-inactivated epidermis. Furthermore, in epidermis-specific Mettl4-inactivated mice, the epidermis was detached from the dermis and presented a phenotype similar to junctional epidermolysis bullosa (JEB), which may result from hemidesmosomes damage (decrease of COL17A1, ITGB4 and ITGA6). Knockdown of Mettl14 in HaCaT cells impaired the self-renewal and decreased the protein level of COL17A1, ITGB4 and ITGA6 and Itgβ4 knockdown inhibited colony formation.

Conclusion

Our study highlighted the role of METTL14 in the maintenance of epidermal homeostasis and identified its critical role through m⁶A-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.

背景:n6 -甲基腺苷(n6 - methylladenosine, m6A)是真核生物mrna中最丰富、最可逆的修饰，但其在哺乳动物表皮发育中的功能尚未完全阐明。目的:探讨m6A甲基转移酶之一METTL14 (Methyltransferase like 14)在维持表皮稳态中的作用。方法:构建表皮基底细胞mettl14失活小鼠。H&E染色和免疫荧光染色探讨表型。为了探索潜在的机制，我们对野生型和mettl14失活的表皮角质形成细胞进行了RNA-seq、核糖体分析和MeRIP-seq。此外，HaCaT细胞用于体外验证。结果:小鼠表皮中Mettl14的失活导致表皮短暂增厚和表皮干细胞池耗竭。有趣的是，我们发现XVII型胶原蛋白(Col17a1)、整合素β4 (Itgβ4)和α6 (Itgα6)的mRNA存在m6A修饰，并且在mettl14失活的表皮中表达减少。此外，在表皮特异性mettl4灭活小鼠中，表皮与真皮分离，呈现类似于交界性大泡表皮松解症(JEB)的表型，这可能是由半半粒损伤(COL17A1、ITGB4和ITGA6减少)引起的。敲低Mettl14抑制HaCaT细胞自我更新，降低COL17A1、ITGB4和ITGA6蛋白水平，敲低Itgβ4抑制集落形成。结论:我们的研究强调了METTL14在维持表皮稳态中的作用，并通过m6a介导的Col17a1、Itgβ4和Itgα6的翻译抑制确定了其关键作用。我们的研究表明，METTL14可能是治疗半染色体缺陷疾病(如JEB)的潜在治疗靶点。

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引用次数: 0

Bath-psoralen plus UVA therapy changes inflammatory proteomic signatures for systemic effects beyond the skin 沐浴补骨脂素加UVA疗法改变炎症蛋白质组学特征，对皮肤以外的系统性影响。

IF 4.6

Journal of dermatological science

Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.09.004

Yoshifumi Kanayama, Kyoko Ikumi, Mai Sakurai, Yuki Enomoto, Emi Nishida, Aya Yamamoto, Akimichi Morita

引用次数: 0

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