Journal of dermatological science最新文献

英文中文

Cyclin E1 is dispensable for skin homeostasis and hyperplasia but is essential for carcinogenesis 细胞周期蛋白E1对皮肤稳态和增生是必不可少的，但对癌变是必不可少的。

IF 4.6

Journal of dermatological science

Pub Date : 2026-01-01 DOI: 10.1016/j.jdermsci.2025.11.001

Lizbeth Contreras , Ana Marcos-Díaz , Lorena García-Gaipo , Berta Casar , Alberto Gandarillas

Background

Epidermal renewal needs tight control of the cell cycle and proliferation to face the continuous mutagenic pressure of UV light. Cyclin E1 is a key molecule in human epidermis, a main driver of the cell cycle and is frequently deregulated in cancer. Both Cyclin E1 and the homologue Cyclin E2 were shown generally dispensable for normal development and growth. However, their requirement for skin hyperplasia and squamous carcinogenesis was unknown.

Objective

We aimed to investigate the requirement of Cyclin E for skin homeostasis, hyperplasia and carcinogenesis.

Methods

We studied the skin and isolated keratinocytes in the absence of Cyclin E1. We analysed steady-state and hyperplastic defective epidermis and monitored carcinogen-induced skin carcinogenesis.

Results

Cyclin E1-defective skin displayed normal histology and function. The epidermis displayed no differences in the capacity to boost proliferation after induction of hyperplasia. However, the lack of the cyclin strikingly overrode carcinogen-induced tumourigenesis. The absence of Cyclin E1 was not compensated by a rise of Cyclin A, another CDK2 potential regulator. Instead, Cyclin E2 was up-regulated in steady-state and hyperplastic skin, providing compensatory potential. However, we did not detect Cyclin E2 in most wild type tumours, especially in the less differentiated carcinomas.

Conclusion

Contrary to the situation in normal development, the results show that either Cyclin E1 or Cyclin E2 is essential for tumorigenesis. They also suggest that in the absence of Cyclin E1, Cyclin E2 serves homeostasis, whereas the oncogenic pathways suppress this compensation as an anti-tumour, self-preserve mechanism.

背景：表皮更新需要严格控制细胞周期和增殖以应对紫外线的持续诱变压力。细胞周期蛋白E1是人类表皮的关键分子，是细胞周期的主要驱动因素，在癌症中经常被解除调控。Cyclin E1和同系物Cyclin E2在正常的发育和生长中通常是不可缺少的。然而，它们对皮肤增生和鳞状癌的需求尚不清楚。目的：探讨细胞周期蛋白E在皮肤稳态、增生和癌变中的作用。方法：在缺乏Cyclin E1的情况下，对皮肤和分离的角质形成细胞进行研究。我们分析了稳态和增生性缺陷表皮，并监测了致癌物诱导的皮肤癌变。结果：Cyclin e1缺陷皮肤组织和功能正常。诱导增生后，表皮促进增殖的能力没有差异。然而，细胞周期蛋白的缺乏显著地压倒了致癌物质诱导的肿瘤发生。Cyclin E1的缺失并没有被另一个CDK2的潜在调节因子Cyclin a的升高所补偿。相反，Cyclin E2在稳态和增生性皮肤中上调，提供代偿电位。然而，我们没有在大多数野生型肿瘤中检测到Cyclin E2，特别是在低分化癌中。结论：与正常发育的情况相反，Cyclin E1或Cyclin E2在肿瘤发生中都是必需的。他们还表明，在缺乏Cyclin E1的情况下，Cyclin E2起着维持体内平衡的作用，而作为一种抗肿瘤的自我保护机制，致癌途径抑制了这种补偿。

{"title":"Cyclin E1 is dispensable for skin homeostasis and hyperplasia but is essential for carcinogenesis","authors":"Lizbeth Contreras , Ana Marcos-Díaz , Lorena García-Gaipo , Berta Casar , Alberto Gandarillas","doi":"10.1016/j.jdermsci.2025.11.001","DOIUrl":"10.1016/j.jdermsci.2025.11.001","url":null,"abstract":"<div><h3>Background</h3><div>Epidermal renewal needs tight control of the cell cycle and proliferation to face the continuous mutagenic pressure of UV light. Cyclin E1 is a key molecule in human epidermis, a main driver of the cell cycle and is frequently deregulated in cancer. Both Cyclin E1 and the homologue Cyclin E2 were shown generally dispensable for normal development and growth. However, their requirement for skin hyperplasia and squamous carcinogenesis was unknown.</div></div><div><h3>Objective</h3><div>We aimed to investigate the requirement of Cyclin E for skin homeostasis, hyperplasia and carcinogenesis.</div></div><div><h3>Methods</h3><div>We studied the skin and isolated keratinocytes in the absence of Cyclin E1. We analysed steady-state and hyperplastic defective epidermis and monitored carcinogen-induced skin carcinogenesis.</div></div><div><h3>Results</h3><div>Cyclin E1-defective skin displayed normal histology and function. The epidermis displayed no differences in the capacity to boost proliferation after induction of hyperplasia. However, the lack of the cyclin strikingly overrode carcinogen-induced tumourigenesis. The absence of Cyclin E1 was not compensated by a rise of Cyclin A, another CDK2 potential regulator. Instead, Cyclin E2 was up-regulated in steady-state and hyperplastic skin, providing compensatory potential. However, we did not detect Cyclin E2 in most wild type tumours, especially in the less differentiated carcinomas.</div></div><div><h3>Conclusion</h3><div>Contrary to the situation in normal development, the results show that either Cyclin E1 or Cyclin E2 is essential for tumorigenesis. They also suggest that in the absence of Cyclin E1, Cyclin E2 serves homeostasis, whereas the oncogenic pathways suppress this compensation as an anti-tumour, self-preserve mechanism.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 1","pages":"Pages 1-10"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558527","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}

引用次数: 0

Adenosine A2A receptors are expressed on the bottom of basal keratinocytes and promote keratinocyte proliferation in human skin 腺苷A2A受体在人皮肤基底角质形成细胞底部表达，促进角质形成细胞增殖。

IF 4.6

Journal of dermatological science

Pub Date : 2026-01-01 DOI: 10.1016/j.jdermsci.2025.11.002

Kazuki Takagaki, Shinobu Nakanishi

引用次数: 0

IF 4.6

Journal of dermatological science

Pub Date : 2026-01-01

引用次数: 0

IF 4.6

Journal of dermatological science

Pub Date : 2026-01-01

引用次数: 0

IF 4.6

Journal of dermatological science

Pub Date : 2026-01-01

引用次数: 0

IF 4.6

Journal of dermatological science

Pub Date : 2026-01-01

引用次数: 0

Comparative analysis of cytotoxic mediators in Stevens-Johnson syndrome and toxic epidermal necrolysis using ex vivo human epidermis. Stevens-Johnson综合征细胞毒性介质与体外人表皮中毒性坏死松解的比较分析。

IF 4.6

Journal of dermatological science

Pub Date : 2025-12-29 DOI: 10.1016/j.jdermsci.2025.12.002

Manao Kinoshita, Youichi Ogawa, Yuka Nagasaka, Andrew Gibson, Ramesh Ram, Shinji Shimada, Akira Momosawa, Elizabeth J Phillips, Riichiro Abe, Tatsuyoshi Kawamura

引用次数: 0

Integrative analysis of bulk multiomics and single-cell transcriptomics reveals the value of neddylation in Skin Cutaneous Melanoma. 大量多组学和单细胞转录组学的综合分析揭示了类化修饰在皮肤黑色素瘤中的价值。

IF 4.6

Journal of dermatological science

Pub Date : 2025-12-27 DOI: 10.1016/j.jdermsci.2025.12.003

Li Yang, Yuan Yao, Kexin Shi, Jun Tian, Lei Zhang

Background: Melanoma is recognized as the most aggressive type of skin cancer, characterized by its high mortality rates and significant therapeutic challenges.

Objective: The primary aim of this research is to analyze cellular heterogeneity in SKCM through single-cell RNA sequencing (scRNA-seq) and construct a neddylation-related prognostic model.

Methods: The scRNA-seq and bulk data of Skin Cutaneous Melanoma (SKCM) samples were obtained from Gene Expression Omnibus and Cancer Genome Atlas Program databases. The nonnegative matrix factorization clustering algorithm was employed to stratify malignant cells into different neddylation cell subtypes in SKCM.

Results: The scRNA-seq analysis classified 31,894 high-quality cells into eight major cell types, revealing significant cellular distribution patterns within the TME. We observed that neddylation activity was significantly elevated in SKCM tissues compared to normal counterparts. Based on the expression profile of prognostic NRGs, the malignant cells were stratified into four neddylation cell subtypes in SKCM. A neddylation-related prognostic signature (NRPS) was established based on marker genes of neddylation-C3 cell subtype. The low-risk group activated immune-related signaling pathways, while the high-risk group activated various cancer-related pathways. Notably, the low-risk group exhibited better overall survival, higher immune cell infiltration, and response rates to immunotherapy compared to the high-risk group.

Conclusion: This investigation emphasizes the crucial function of NRGs in the prognosis of SKCM, while also underscoring the importance of understanding the TME and its cellular heterogeneity. The distinct cellular composition and functional attributes within the TME highlight the potential for immunotherapy responses that can be stratified by risk.

背景：黑色素瘤是公认的最具侵袭性的皮肤癌类型，其特点是高死亡率和显著的治疗挑战。目的：本研究的主要目的是通过单细胞RNA测序（scRNA-seq）分析SKCM的细胞异质性，并构建类化修饰相关的预后模型。方法：皮肤黑色素瘤（SKCM）样本的scRNA-seq和大量数据来自基因表达Omnibus和癌症基因组图谱计划数据库。采用非负矩阵分解聚类算法将SKCM恶性细胞分层为不同的类化细胞亚型。结果：scRNA-seq分析将31894个高质量细胞分为8种主要细胞类型，揭示了TME内显著的细胞分布模式。我们观察到，与正常组织相比，SKCM组织中的类黄酮化活性显著升高。根据预后NRGs的表达谱，将SKCM恶性细胞分为4种类化细胞亚型。基于类化修饰- c3细胞亚型的标记基因，建立了类化修饰相关的预后特征（NRPS）。低危组激活了免疫相关的信号通路，而高危组激活了各种癌症相关的信号通路。值得注意的是，与高风险组相比，低风险组表现出更好的总生存率，更高的免疫细胞浸润和免疫治疗应答率。结论：本研究强调了NRGs在SKCM预后中的重要作用，同时也强调了了解TME及其细胞异质性的重要性。TME内独特的细胞组成和功能属性突出了可按风险分层的免疫治疗反应的潜力。

{"title":"Integrative analysis of bulk multiomics and single-cell transcriptomics reveals the value of neddylation in Skin Cutaneous Melanoma.","authors":"Li Yang, Yuan Yao, Kexin Shi, Jun Tian, Lei Zhang","doi":"10.1016/j.jdermsci.2025.12.003","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.12.003","url":null,"abstract":"<p><strong>Background: </strong>Melanoma is recognized as the most aggressive type of skin cancer, characterized by its high mortality rates and significant therapeutic challenges.</p><p><strong>Objective: </strong>The primary aim of this research is to analyze cellular heterogeneity in SKCM through single-cell RNA sequencing (scRNA-seq) and construct a neddylation-related prognostic model.</p><p><strong>Methods: </strong>The scRNA-seq and bulk data of Skin Cutaneous Melanoma (SKCM) samples were obtained from Gene Expression Omnibus and Cancer Genome Atlas Program databases. The nonnegative matrix factorization clustering algorithm was employed to stratify malignant cells into different neddylation cell subtypes in SKCM.</p><p><strong>Results: </strong>The scRNA-seq analysis classified 31,894 high-quality cells into eight major cell types, revealing significant cellular distribution patterns within the TME. We observed that neddylation activity was significantly elevated in SKCM tissues compared to normal counterparts. Based on the expression profile of prognostic NRGs, the malignant cells were stratified into four neddylation cell subtypes in SKCM. A neddylation-related prognostic signature (NRPS) was established based on marker genes of neddylation-C3 cell subtype. The low-risk group activated immune-related signaling pathways, while the high-risk group activated various cancer-related pathways. Notably, the low-risk group exhibited better overall survival, higher immune cell infiltration, and response rates to immunotherapy compared to the high-risk group.</p><p><strong>Conclusion: </strong>This investigation emphasizes the crucial function of NRGs in the prognosis of SKCM, while also underscoring the importance of understanding the TME and its cellular heterogeneity. The distinct cellular composition and functional attributes within the TME highlight the potential for immunotherapy responses that can be stratified by risk.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013820","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}

引用次数: 0

Transcriptional regulation of Mlph and Rab27a by PAX3-NF-κB interaction in melanosome transport of melanocytes PAX3-NF-κB相互作用对黑色素细胞黑素体转运中Mlph和Rab27a的转录调控。

IF 4.6

Journal of dermatological science

Pub Date : 2025-12-01 DOI: 10.1016/j.jdermsci.2025.10.001

HaiRu Zhao , SeongWon Park , ChanSong Jo, JeongMi Lee, JaeSung Hwang

Background

Melanosome transport is a highly coordinated process involving both microtubule- and actin-dependent mechanisms. Our previous study identified 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO) as an inhibitor of melanosome transport. In the present study, we aimed to elucidate the transcriptional regulation of melanosome transport by identifying the key transcription factors involved in this process.

Objective

This study investigates the regulation of NF-κB by PAX3 and its role in binding to the enhancer regions of Rab27a and Mlph to modulate melanosome transport.

Methods

Mouse melanocytes were transfected with Pax3-specific siRNA (siPAX3), followed by the assessment of melanosome aggregation. NF-κB expression was analyzed using Western blot and RT-PCR. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) were performed to determine NF-κB binding to the enhancer regions of Rab27a and Mlph.

Results

Silencing of PAX3 significantly impaired melanosome transport, leading to the intracellular accumulation of melanosomes. Moreover, PAX3 knockdown markedly decreased the expression levels of Mlph and Rab27a. ChIP and EMSA assays further demonstrated that NF-κB directly binds to the enhancer regions of Rab27a (+51,608 to +51,619 bp relative to the TSS) and Mlph (+34,021 to +34,033 bp relative to the TSS).

Conclusion

This study provides the first evidence of a regulatory relationship between PAX3 and NF-κB, wherein NF-κB directly binds to the enhancer regions of Rab27a and Mlph to modulate melanosome transport. These findings offer novel insights into the transcriptional control of melanogenesis and its potential implications for melanoma research.

背景：黑素小体转运是一个高度协调的过程，涉及微管和动作蛋白依赖机制。我们之前的研究发现2-甲基萘酚[1,2,3-de]喹啉-8- 1 （MNQO）是黑色素小体运输的抑制剂。在本研究中，我们旨在通过确定参与该过程的关键转录因子来阐明黑素小体转运的转录调控。目的：探讨PAX3对NF-κB的调控作用及其与Rab27a和Mlph增强区结合调节黑素小体转运的作用。方法：用pax3特异性siRNA （siPAX3）转染小鼠黑素细胞，观察黑素小体聚集情况。采用Western blot和RT-PCR分析NF-κB的表达。采用染色质免疫沉淀法（ChIP）和电泳迁移量转移法（EMSA）检测NF-κB与Rab27a和Mlph增强子区的结合。结果：PAX3的沉默显著损害了黑素小体的运输，导致黑素小体在细胞内积聚。此外，PAX3敲低可显著降低Mlph和Rab27a的表达水平。ChIP和EMSA进一步证实，NF-κB直接结合Rab27a（相对于TSS +51,608 ~ +51,619 bp）和Mlph（相对于TSS +34,021 ~ +34,033 bp）的增强子区域。结论：本研究首次证明了PAX3与NF-κB之间存在调控关系，NF-κB直接结合Rab27a和Mlph的增强子区，调节黑素小体的转运。这些发现为黑素生成的转录控制及其对黑色素瘤研究的潜在影响提供了新的见解。

{"title":"Transcriptional regulation of Mlph and Rab27a by PAX3-NF-κB interaction in melanosome transport of melanocytes","authors":"HaiRu Zhao , SeongWon Park , ChanSong Jo, JeongMi Lee, JaeSung Hwang","doi":"10.1016/j.jdermsci.2025.10.001","DOIUrl":"10.1016/j.jdermsci.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Melanosome transport is a highly coordinated process involving both microtubule- and actin-dependent mechanisms. Our previous study identified 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO) as an inhibitor of melanosome transport. In the present study, we aimed to elucidate the transcriptional regulation of melanosome transport by identifying the key transcription factors involved in this process.</div></div><div><h3>Objective</h3><div>This study investigates the regulation of <em>NF-κB</em> by <em>PAX3</em> and its role in binding to the enhancer regions of <em>Rab27a</em> and <em>Mlph</em> to modulate melanosome transport.</div></div><div><h3>Methods</h3><div>Mouse melanocytes were transfected with Pax3-specific siRNA (si<em>PAX3</em>), followed by the assessment of melanosome aggregation. <em>NF-κB</em> expression was analyzed using Western blot and RT-PCR. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) were performed to determine NF-κB binding to the enhancer regions of Rab27a and Mlph.</div></div><div><h3>Results</h3><div>Silencing of P<em>AX3</em> significantly impaired melanosome transport, leading to the intracellular accumulation of melanosomes. Moreover, <em>PAX3</em> knockdown markedly decreased the expression levels of <em>Mlph</em> and <em>Rab27a</em>. ChIP and EMSA assays further demonstrated that <em>NF-κB</em> directly binds to the enhancer regions of <em>Rab27a</em> (+51,608 to +51,619 bp relative to the TSS) and <em>Mlph</em> (+34,021 to +34,033 bp relative to the TSS).</div></div><div><h3>Conclusion</h3><div>This study provides the first evidence of a regulatory relationship between <em>PAX3</em> and <em>NF-κB</em>, wherein <em>NF-κB</em> directly binds to the enhancer regions of <em>Rab27a</em> and <em>Mlph</em> to modulate melanosome transport. These findings offer novel insights into the transcriptional control of melanogenesis and its potential implications for melanoma research.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 3","pages":"Pages 98-104"},"PeriodicalIF":4.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145369186","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}

引用次数: 0

Three-dimensional cultured human skin model replicating a human facial shape enables personalized assessment of UVB damage in various facial areas 复制人体面部形状的三维培养人体皮肤模型可以个性化评估UVB在不同面部区域的损伤。

IF 4.6

Journal of dermatological science

Pub Date : 2025-12-01 DOI: 10.1016/j.jdermsci.2025.10.002

Katsuma Miyachi , Takaaki Yamada , Takeru Siraishi , Toshio Igarashi , Ryosuke Okuno , Yuichi Hasebe , Osamu Hirose , Seiji Hasegawa

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Journal of dermatological science

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀