Journal of dermatological science最新文献

英文中文

A signal peptide variant in SLURP1 with dominant-negative effect causes progressive symmetric erythrokeratodermia SLURP1的信号肽变异具有显性阴性作用，可导致进行性对称红角化皮病。

IF 4.6

Journal of dermatological science

Pub Date : 2025-04-01 DOI: 10.1016/j.jdermsci.2025.02.006

Zhuoqing Gong , Yunran Peng , Sisi Zhao , Zhimiao Lin , Zhanli Tang , Huijun Wang

Background

Progressive symmetric erythrokeratodermia (PSEK) is a group of hereditary cornification disorders characterized by symmetrical, progressive erythroderma and hyperkeratosis over the body. Loss-of-function variants in SLURP1, encoding secreted Ly-6/uPAR-related protein 1, is known to cause Mal de Meleda, an autosomal recessive palmoplantar keratoderma.

Objective

To identify the genetic basis and the pathogenesis of a sporadic patient with PSEK.

Methods

Whole-exome sequencing and Sanger sequencing were performed to identify the pathogenic variant(s). The expression of SLURP1 was assessed on the patient’s skin tissue by immunofluorescence. Western blotting (WB) and immunofluorescence (IF) were performed on eukaryotic overexpression systems to evaluate the signal peptide (SP) cleavage, subcellular localization and secretion of the mutant SLURP1. Combined WB and IF analyses were conducted on cells co-transfected with FLAG-tagged wild-type SLURP1 and untagged SLURP1-Ala22Asp.

Results

We identified a de novo heterozygous variant in SLURP1 (c.65A > C, p.Ala22Asp) affecting the first residue before SP cleavage site in a patient with PSEK. This variant abolished the cleavage site of SP, resulting in translocation deficiency to the Golgi apparatus and decreased secretion of the mutant SLURP1. We also found that the SLURP1-Ala22Asp exerted a dominant-negative effect by impeding the SP cleavage of the wild-type SLURP1 and affecting its subcellular localization and secretion in a dose-dependent manner.

Conclusion

We reported the first autosomal-dominant variant in SLURP1 associated with a new phenotype of PSEK in a patient, emphasizing the genetic and clinical heterogeneity of SLURP1-associated genodermatoses.

背景：进行性对称红皮病（PSEK）是一组遗传性角化疾病，其特征是全身对称、进行性红皮病和角化过度。SLURP1编码分泌的Ly-6/ upar相关蛋白1，已知其功能缺失变异可导致掌足底角化病（Mal de Meleda）。目的：探讨散发性PSEK患者的遗传基础和发病机制。方法：采用全外显子组测序和Sanger测序鉴定致病变异。免疫荧光法检测患者皮肤组织中SLURP1的表达。利用Western blotting （WB）和免疫荧光（IF）对真核过表达系统进行检测，评估突变体SLURP1的信号肽（SP）裂解、亚细胞定位和分泌情况。对共转染flag标记的野生型SLURP1和未标记的SLURP1- ala22asp的细胞进行WB和IF联合分析。结果：我们发现了一个新的SLURP1杂合变异（C . 65a > C, p.Ala22Asp），影响PSEK患者SP切割位点前的第一个残基。该变异消除了SP的裂解位点，导致高尔基体易位不足，突变体SLURP1的分泌减少。我们还发现SLURP1- ala22asp通过阻断野生型SLURP1的SP切割，并以剂量依赖的方式影响其亚细胞定位和分泌，从而发挥显性负向作用。结论：我们报道了一例患者中与PSEK新表型相关的SLURP1常染色体显性变异，强调了SLURP1相关的遗传性皮肤病的遗传和临床异质性。

{"title":"A signal peptide variant in SLURP1 with dominant-negative effect causes progressive symmetric erythrokeratodermia","authors":"Zhuoqing Gong , Yunran Peng , Sisi Zhao , Zhimiao Lin , Zhanli Tang , Huijun Wang","doi":"10.1016/j.jdermsci.2025.02.006","DOIUrl":"10.1016/j.jdermsci.2025.02.006","url":null,"abstract":"<div><h3>Background</h3><div>Progressive symmetric erythrokeratodermia (PSEK) is a group of hereditary cornification disorders characterized by symmetrical, progressive erythroderma and hyperkeratosis over the body. Loss-of-function variants in <em>SLURP1</em>, encoding secreted Ly-6/uPAR-related protein 1, is known to cause Mal de Meleda, an autosomal recessive palmoplantar keratoderma.</div></div><div><h3>Objective</h3><div>To identify the genetic basis and the pathogenesis of a sporadic patient with PSEK.</div></div><div><h3>Methods</h3><div>Whole-exome sequencing and Sanger sequencing were performed to identify the pathogenic variant(s). The expression of SLURP1 was assessed on the patient’s skin tissue by immunofluorescence. Western blotting (WB) and immunofluorescence (IF) were performed on eukaryotic overexpression systems to evaluate the signal peptide (SP) cleavage, subcellular localization and secretion of the mutant SLURP1. Combined WB and IF analyses were conducted on cells co-transfected with FLAG-tagged wild-type SLURP1 and untagged SLURP1-Ala22Asp.</div></div><div><h3>Results</h3><div>We identified a <em>de novo</em> heterozygous variant in <em>SLURP1</em> (c.65A > C, p.Ala22Asp) affecting the first residue before SP cleavage site in a patient with PSEK. This variant abolished the cleavage site of SP, resulting in translocation deficiency to the Golgi apparatus and decreased secretion of the mutant SLURP1. We also found that the SLURP1-Ala22Asp exerted a dominant-negative effect by impeding the SP cleavage of the wild-type SLURP1 and affecting its subcellular localization and secretion in a dose-dependent manner.</div></div><div><h3>Conclusion</h3><div>We reported the first autosomal-dominant variant in <em>SLURP1</em> associated with a new phenotype of PSEK in a patient, emphasizing the genetic and clinical heterogeneity of <em>SLURP1</em>-associated genodermatoses.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 1","pages":"Pages 38-44"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538267","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

Topical sirolimus suppresses skin fibrosis in a bleomycin-induced mouse model of systemic sclerosis 局部西罗莫司抑制博来霉素诱导的系统性硬化症小鼠模型的皮肤纤维化。

IF 4.6

Journal of dermatological science

Pub Date : 2025-04-01 DOI: 10.1016/j.jdermsci.2025.02.002

Akiko Sekiguchi , Mai Ishikawa , Akihiko Uchiyama, Yoko Yokoyama, Sachiko Ogino, Ryoko Torii, Sei-ichiro Motegi

引用次数: 0

Thiotaurine inhibits melanoma progression by enhancing Ca2+ overload-induced cellular apoptosis 硫代牛磺酸通过增强 Ca2+ 超载诱导的细胞凋亡抑制黑色素瘤的发展。

IF 4.6

Journal of dermatological science

Pub Date : 2025-04-01 DOI: 10.1016/j.jdermsci.2025.03.001

Di Wang , Ansheng Xie , Jialiang Luo , Lei Li , Zhiwen Zhang , Weiwei Deng , Bin Yang , Yuan Chang , Yunsheng Liang

Background

Melanoma is the most dangerous type of skin cancer with poor therapy outcomes. Since malignant cells are more susceptible to Ca²⁺ overload than normal cells, activating Ca²⁺ overload-mediated apoptosis may be a promising strategy to inhibit melanoma progression. Hydrogen sulfide (H₂S) donors can regulate Ca²⁺ channels, but their effects on melanoma cells remain unclear.

Objective

To explore the effects of Thiotaurine (TTAU), an H₂S donor, on melanoma cells and its underlying mechanisms.

Methods

We tested the effect of TTAU by culturing melanoma cells in vitro and establishing the xenograft model of mice in vivo. Cell proliferation and apoptosis were assessed using the CCK-8 test and flow cytometry. Molecules involved in apoptosis or Ca²⁺-related signal transduction were analyzed by western blotting. Immunofluorescence was used to measure Ca²⁺ levels, mitochondrial damage, and reactive oxygen species (ROS).

Results

TTAU significantly reduced melanoma cell viability and induced apoptosis both in vitro and in vivo. Mechanistically, TTAU increased intracellular Ca²⁺, upregulated transient receptor potential vanilloid 1(TRPV1), and decreased activating transcription factor 3(ATF3) by nuclear factor of activated T cell cytoplasmic 1(NFATc1). TTAU also caused mitochondrial damage and ROS overproduction, which also promoted apoptosis.

Conclusion

We first elucidate that TTAU inhibits melanoma progression by activating Ca²⁺ influx-NFATc1-ATF3 signaling and aggravating mitochondrial oxidative stress, in which TRPV1 may act as an amplifier for Ca²⁺ influx. Our research is expected to provide new ideas for the treatment of tumors such as melanoma, as well as the clinical application of reactive sulfur species-based drugs.

背景：黑色素瘤是最危险的皮肤癌类型，治疗效果差。由于恶性细胞比正常细胞更容易受到Ca2+超载的影响，激活Ca2+超载介导的细胞凋亡可能是抑制黑色素瘤进展的一种有希望的策略。硫化氢（H2S）供体可以调节Ca2+通道，但其对黑色素瘤细胞的影响尚不清楚。目的：探讨硫化氢供体硫牛磺酸（Thiotaurine， TTAU）对黑色素瘤细胞的作用及其机制。方法：通过体外培养黑色素瘤细胞和建立小鼠体内异种移植瘤模型，验证TTAU的作用。采用CCK-8检测和流式细胞术检测细胞增殖和凋亡情况。western blotting分析参与细胞凋亡或Ca2+相关信号转导的分子。免疫荧光用于测量Ca2+水平，线粒体损伤和活性氧（ROS）。结果：TTAU在体外和体内均能显著降低黑色素瘤细胞活力，诱导细胞凋亡。在机制上，TTAU增加了细胞内Ca2+，上调了瞬时受体电位香兰素1(TRPV1)，并通过活化T细胞质1的核因子（NFATc1）降低了活化转录因子3（ATF3）。TTAU还引起线粒体损伤和ROS过量产生，从而促进细胞凋亡。结论：我们首先阐明了TTAU通过激活Ca2+流入- nfatc1 - atf3信号和加重线粒体氧化应激来抑制黑色素瘤的进展，其中TRPV1可能作为Ca2+流入的放大器。我们的研究有望为黑色素瘤等肿瘤的治疗以及活性硫类药物的临床应用提供新的思路。

{"title":"Thiotaurine inhibits melanoma progression by enhancing Ca2+ overload-induced cellular apoptosis","authors":"Di Wang , Ansheng Xie , Jialiang Luo , Lei Li , Zhiwen Zhang , Weiwei Deng , Bin Yang , Yuan Chang , Yunsheng Liang","doi":"10.1016/j.jdermsci.2025.03.001","DOIUrl":"10.1016/j.jdermsci.2025.03.001","url":null,"abstract":"<div><h3>Background</h3><div>Melanoma is the most dangerous type of skin cancer with poor therapy outcomes. Since malignant cells are more susceptible to Ca<sup>2+</sup> overload than normal cells, activating Ca<sup>2+</sup> overload-mediated apoptosis may be a promising strategy to inhibit melanoma progression. Hydrogen sulfide (H<sub>2</sub>S) donors can regulate Ca<sup>2+</sup> channels, but their effects on melanoma cells remain unclear.</div></div><div><h3>Objective</h3><div>To explore the effects of Thiotaurine (TTAU), an H<sub>2</sub>S donor, on melanoma cells and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>We tested the effect of TTAU by culturing melanoma cells in vitro and establishing the xenograft model of mice in vivo. Cell proliferation and apoptosis were assessed using the CCK-8 test and flow cytometry. Molecules involved in apoptosis or Ca<sup>2+</sup>-related signal transduction were analyzed by western blotting. Immunofluorescence was used to measure Ca<sup>2+</sup> levels, mitochondrial damage, and reactive oxygen species (ROS).</div></div><div><h3>Results</h3><div>TTAU significantly reduced melanoma cell viability and induced apoptosis both in vitro and in vivo. Mechanistically, TTAU increased intracellular Ca<sup>2+</sup>, upregulated transient receptor potential vanilloid 1(TRPV1), and decreased activating transcription factor 3(ATF3) by nuclear factor of activated T cell cytoplasmic 1(NFATc1). TTAU also caused mitochondrial damage and ROS overproduction, which also promoted apoptosis.</div></div><div><h3>Conclusion</h3><div>We first elucidate that TTAU inhibits melanoma progression by activating Ca<sup>2+</sup> influx-NFATc1-ATF3 signaling and aggravating mitochondrial oxidative stress, in which TRPV1 may act as an amplifier for Ca<sup>2+</sup> influx. Our research is expected to provide new ideas for the treatment of tumors such as melanoma, as well as the clinical application of reactive sulfur species-based drugs.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 1","pages":"Pages 29-37"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797289","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

Triclosan exacerbates atopic dermatitis in mouse models via thymic stromal lymphopoietin 三氯生通过胸腺基质淋巴生成素加重小鼠模型中的特应性皮炎。

IF 4.6

Journal of dermatological science

Pub Date : 2025-04-01 DOI: 10.1016/j.jdermsci.2025.02.007

Marie Charlotte Schuppe , Patryk Porebski , Katharina Klara Hahn , Kexin Liao , Anja Uhmann , Andrea Braun , Prasad Dasari , Michael Peter Schön , Timo Buhl

Background

Triclosan, a common antimicrobial agent, is widely used in personal-care products and as a topical antiseptic in atopic dermatitis (AD).

Objective

This study aimed to evaluate the topical and systemic effect of triclosan on AD in murine models, with a specific focus on the role of thymic stromal lymphopoietin (TSLP).

Methods

AD-like skin disease was induced by topical application of MC903 and house dust mites in female wildtype BALB/c, C57BL/6 J, and TSLP receptor (TSLPR)-knockout mouse strains. Mice were treated with triclosan both topically and systemically. Skin inflammation was assessed by measuring ear thickness. Infiltration of immune cells was analyzed by flow cytometry and immunohistochemistry (IHC). Cytokine expression was determined by quantitative real-time PCR.

Results

Triclosan application induced skin inflammation in a dose-dependent manner. Topical triclosan treatment increased ear inflammation and immune cell infiltration in AD-like mouse models. Systemic administration of triclosan also enhanced local AD-like skin reactions. Triclosan-induced skin inflammation was reduced in TSLP-receptor-knockout mice or by blocking TSLP, thus indicating the pivotal role of TSLP in mediating the immunological effects of triclosan.

Conclusions

Topical and systemic administration of triclosan exacerbates AD-like skin inflammation in murine models, with TSLP being a central mediator of this process. The translational relevance of these findings to human disease remains uncertain, as no direct human data are available.

背景：三氯生是一种常见的抗菌药物，广泛应用于个人护理产品和特应性皮炎（AD）的局部抗菌剂。目的：本研究旨在评估三氯生对小鼠AD模型的局部和全身作用，特别关注胸腺基质淋巴生成素（TSLP）的作用。方法：对BALB/c、C57BL/6 J和TSLP受体（TSLPR）敲除的雌性野生型小鼠，局部应用MC903和室内尘螨诱导ad样皮肤病。小鼠局部和全身给予三氯生治疗。通过测量耳部厚度来评估皮肤炎症。采用流式细胞术和免疫组织化学（IHC）分析免疫细胞浸润情况。实时荧光定量PCR检测细胞因子表达。结果：应用三氯生诱导皮肤炎症呈剂量依赖性。局部三氯生治疗增加ad样小鼠模型的耳部炎症和免疫细胞浸润。全身给药三氯生也增强了局部ad样皮肤反应。TSLP受体敲除小鼠或通过阻断TSLP可减轻三氯生诱导的皮肤炎症，从而提示TSLP在介导三氯生免疫作用中的关键作用。结论：局部和全身给药三氯生加剧了小鼠模型ad样皮肤炎症，TSLP是这一过程的中心介质。这些发现与人类疾病的转化相关性仍然不确定，因为没有直接的人类数据。

{"title":"Triclosan exacerbates atopic dermatitis in mouse models via thymic stromal lymphopoietin","authors":"Marie Charlotte Schuppe , Patryk Porebski , Katharina Klara Hahn , Kexin Liao , Anja Uhmann , Andrea Braun , Prasad Dasari , Michael Peter Schön , Timo Buhl","doi":"10.1016/j.jdermsci.2025.02.007","DOIUrl":"10.1016/j.jdermsci.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Triclosan, a common antimicrobial agent, is widely used in personal-care products and as a topical antiseptic in atopic dermatitis (AD).</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the topical and systemic effect of triclosan on AD in murine models, with a specific focus on the role of thymic stromal lymphopoietin (TSLP).</div></div><div><h3>Methods</h3><div>AD-like skin disease was induced by topical application of MC903 and house dust mites in female wildtype BALB/c, C57BL/6 J, and TSLP receptor (TSLPR)-knockout mouse strains. Mice were treated with triclosan both topically and systemically. Skin inflammation was assessed by measuring ear thickness. Infiltration of immune cells was analyzed by flow cytometry and immunohistochemistry (IHC). Cytokine expression was determined by quantitative real-time PCR.</div></div><div><h3>Results</h3><div>Triclosan application induced skin inflammation in a dose-dependent manner. Topical triclosan treatment increased ear inflammation and immune cell infiltration in AD-like mouse models. Systemic administration of triclosan also enhanced local AD-like skin reactions. Triclosan-induced skin inflammation was reduced in TSLP-receptor-knockout mice or by blocking TSLP, thus indicating the pivotal role of TSLP in mediating the immunological effects of triclosan.</div></div><div><h3>Conclusions</h3><div>Topical and systemic administration of triclosan exacerbates AD-like skin inflammation in murine models, with TSLP being a central mediator of this process. The translational relevance of these findings to human disease remains uncertain, as no direct human data are available.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 1","pages":"Pages 1-8"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588750","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

Rapid thawing enhances tissue destruction in a mouse model of cutaneous cryoablation: Insights into oxidative stress and neutrophil activation 快速解冻增强皮肤冷冻消融小鼠模型中的组织破坏：氧化应激和中性粒细胞激活的见解。

IF 4.6

Journal of dermatological science

Pub Date : 2025-04-01 DOI: 10.1016/j.jdermsci.2025.02.003

Akiko Sekiguchi , Mai Ishikawa , Akihiko Uchiyama , Yoko Yokoyama , Sachiko Ogino , Ryoko Torii , Ryoko Akai , Takao Iwawaki , Sei-ichiro Motegi

Background

Cryoablation is an integral therapeutic approach in dermatology for eliminating viral warts and benign tumors by damaging tissue through freeze-thaw cycles. Rapid thawing of the frozen area by warming it with fingertips during cryoablation is a common technique in Japan; however, its efficacy has not been elucidated.

Objective

This study aimed to evaluate the effect of rapid thawing on cryoablation-treated skin and clarify the underlying mechanisms using cryoablation model mice.

Methods

Cryoablation was performed on the dorsal skin of mice using a liquid nitrogen-soaked cotton swab, followed by rapid thawing by warming with fingertips or natural thawing without treatment. The effects on skin ulcers, immune cell infiltration, and oxidative stress were assessed.

Results

Rapid thawing enlarged cryoablation-induced skin ulcers. The numbers of cryoablation-induced CD3⁺ T cells, neutrophils, neutrophil extracellular traps (NETs), and TUNEL⁺ cells increased with rapid thawing. Visualization of oxidative stress in OKD48 transgenic mice showed that oxidative stress signals in the cryoablation-treated area were enhanced with rapid thawing. Real-time PCR analysis of mouse skin demonstrated that cryoblation-induced levels of NOX2 and HO-1 were significantly elevated with rapid thawing. In mouse melanoma tumors treated with cryoablation, rapid thawing significantly inhibited tumor growth and increased the infiltration of neutrophils, NETs, and TUNEL⁺ cells compared to the group without rapid thawing.

Conclusion

Rapid thawing during cryoablation enhances neutrophil and lymphocyte infiltration, increases oxidative stress, and induces cell death, leading to greater tissue destruction in mice. Dermatologists should consider employing rapid thawing techniques during cryoablation when higher therapeutic intensities are required.

背景：冷冻消融术是皮肤科通过冻融循环损伤组织来消除病毒性疣和良性肿瘤的一种整体治疗方法。在日本，在冷冻消融过程中，用指尖加热冷冻区域来快速解冻是一种常见的技术；然而，其功效尚未得到阐明。目的：利用冻融模型小鼠，探讨快速解冻对冻融后皮肤的影响，并阐明其作用机制。方法：用液氮棉签对小鼠背部皮肤进行冷冻消融，然后用指尖加热或不加处理的自然解冻快速解冻。评估了对皮肤溃疡、免疫细胞浸润和氧化应激的影响。结果：冻融引起的皮肤溃疡迅速融化。随着快速解冻，冷冻诱导的CD3+ T细胞、中性粒细胞、中性粒细胞胞外陷阱（NETs）和TUNEL+细胞的数量增加。OKD48转基因小鼠的氧化应激可视化显示，冻融处理区氧化应激信号随着快速解冻而增强。对小鼠皮肤进行实时荧光定量PCR分析发现，快速解冻后，小鼠皮肤中NOX2和HO-1水平显著升高。在冷冻消融处理的小鼠黑色素瘤肿瘤中，与未快速解冻组相比，快速解冻显著抑制肿瘤生长，增加中性粒细胞、NETs和TUNEL+细胞的浸润。结论：冻融过程中快速解冻增加了小鼠中性粒细胞和淋巴细胞的浸润，增加了氧化应激，诱导细胞死亡，导致更大的组织破坏。当需要更高的治疗强度时，皮肤科医生应考虑在冷冻消融期间采用快速解冻技术。

{"title":"Rapid thawing enhances tissue destruction in a mouse model of cutaneous cryoablation: Insights into oxidative stress and neutrophil activation","authors":"Akiko Sekiguchi , Mai Ishikawa , Akihiko Uchiyama , Yoko Yokoyama , Sachiko Ogino , Ryoko Torii , Ryoko Akai , Takao Iwawaki , Sei-ichiro Motegi","doi":"10.1016/j.jdermsci.2025.02.003","DOIUrl":"10.1016/j.jdermsci.2025.02.003","url":null,"abstract":"<div><h3>Background</h3><div>Cryoablation is an integral therapeutic approach in dermatology for eliminating viral warts and benign tumors by damaging tissue through freeze-thaw cycles. Rapid thawing of the frozen area by warming it with fingertips during cryoablation is a common technique in Japan; however, its efficacy has not been elucidated.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the effect of rapid thawing on cryoablation-treated skin and clarify the underlying mechanisms using cryoablation model mice.</div></div><div><h3>Methods</h3><div>Cryoablation was performed on the dorsal skin of mice using a liquid nitrogen-soaked cotton swab, followed by rapid thawing by warming with fingertips or natural thawing without treatment. The effects on skin ulcers, immune cell infiltration, and oxidative stress were assessed.</div></div><div><h3>Results</h3><div>Rapid thawing enlarged cryoablation-induced skin ulcers. The numbers of cryoablation-induced CD3<sup>+</sup> T cells, neutrophils, neutrophil extracellular traps (NETs), and TUNEL<sup>+</sup> cells increased with rapid thawing. Visualization of oxidative stress in OKD48 transgenic mice showed that oxidative stress signals in the cryoablation-treated area were enhanced with rapid thawing. Real-time PCR analysis of mouse skin demonstrated that cryoblation-induced levels of NOX2 and HO-1 were significantly elevated with rapid thawing. In mouse melanoma tumors treated with cryoablation, rapid thawing significantly inhibited tumor growth and increased the infiltration of neutrophils, NETs, and TUNEL<sup>+</sup> cells compared to the group without rapid thawing.</div></div><div><h3>Conclusion</h3><div>Rapid thawing during cryoablation enhances neutrophil and lymphocyte infiltration, increases oxidative stress, and induces cell death, leading to greater tissue destruction in mice. Dermatologists should consider employing rapid thawing techniques during cryoablation when higher therapeutic intensities are required.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 1","pages":"Pages 9-17"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506666","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

Editors Choice 编辑的选择

IF 4.6

Journal of dermatological science

Pub Date : 2025-04-01 DOI: 10.1016/S0923-1811(25)00052-0

引用次数: 0

JSID’s Fellowship Shiseido Research Grant JSID奖学金资生堂研究基金

IF 4.6

Journal of dermatological science

Pub Date : 2025-04-01 DOI: 10.1016/S0923-1811(25)00054-4

引用次数: 0

Genetics and epigenetics in vitiligo 白癜风的遗传学和表观遗传学。

IF 4.6

Journal of dermatological science

Pub Date : 2025-03-01 DOI: 10.1016/j.jdermsci.2025.01.004

Ken Okamura, Tamio Suzuki

Vitiligo, a complex autoimmune disorder characterized by melanocyte destruction, arises from an intricate interplay of genetic, epigenetic, immune, and environmental factors. Genome-wide association studies (GWAS) have identified over 50 susceptibility loci, including key genes within the MHC region and those involved in immunity, oxidative stress, and melanogenesis. Concurrently, epigenetic research has unraveled regulatory networks critical to vitiligo pathogenesis, with a focus on DNA methylation and non-coding RNAs (e.g., microRNAs, long non-coding RNAs, and circular RNAs). These advancements provide deeper insights into gene regulation, immune processes, and cellular dynamics. This review integrates findings from genetic and epigenetic studies to offer a comprehensive understanding of molecular mechanisms of vitiligo, paving the way for innovative, personalized therapeutic approaches.

白癜风是一种以黑素细胞破坏为特征的复杂自身免疫性疾病，是遗传、表观遗传、免疫和环境因素复杂相互作用的结果。全基因组关联研究（GWAS）已经确定了50多个易感位点，包括MHC区域内的关键基因以及与免疫、氧化应激和黑色素生成有关的基因。同时，表观遗传学研究揭示了白癜风发病机制的关键调控网络，重点关注DNA甲基化和非编码rna（如microRNAs、长链非编码rna和环状rna）。这些进步为基因调控、免疫过程和细胞动力学提供了更深入的见解。本文综述了遗传学和表观遗传学研究的结果，以提供对白癜风分子机制的全面了解，为创新的个性化治疗方法铺平道路。

引用次数: 0

Cytosolic mtDNA-cGAS-STING axis mediates melanocytes pyroptosis to promote CD8+ T-cell activation in vitiligo 细胞质mtDNA-cGAS-STING轴介导黑色素细胞热解，促进白癜风患者CD8+T细胞的活化。

IF 4.6

Journal of dermatological science

Pub Date : 2025-03-01 DOI: 10.1016/j.jdermsci.2024.12.002

Xinya Xu , Xinhua Lu , Yue Zheng , Yang Xie , Wei Lai

Background

The cGAS-STING axis, a DNA sensor pathway, has recently emerged as a key hub in sensing stress signals and initiating the immune cascade in several diseases. However, its role in the pathogenesis of vitiligo remains unclear.

Objective

To explore the pathogenic role of the cGAS-STING axis in linking oxidative stress and CD8⁺ T-cell-mediated anti-melanocytic immunity in vitiligo.

Methods

The expression status of the cGAS-STING axis and cytosolic mtDNA were evaluated in the oxidatively stressed epidermal cells and vitiligo perilesional skin, respectively. Then, we investigated the activation of cGAS-STING axis in mtDNA-treated melanocytes, and the influence of cGAS or STING silencing on mtDNA-induced melanocytes pyroptosis. Finally, the paracrine effects of melanocytes pyroptosis on CD8⁺ T cell activation were explored.

Results

We initially demonstrated that the cGAS-STING axis in melanocytes was highly susceptible to oxidative stress and activated in the vitiliginous melanocytes of perilesional skin, accompanied by enhanced cytosolic mtDNA accumulation. Our mechanistic in vitro experiments confirmed that oxidative stress-induced mitochondrial damage in epidermal cells led to cytosolic mtDNA accumulation, which served as a trigger in activating the cGAS-STING axis in melanocytes. Furthermore, the cytosolic mtDNA-cGAS-STING axis was verified to mediate melanocytes pyroptosis. More importantly, we found that IL-1β and IL-18 produced by pyroptotic melanocytes promoted the activation of CD8⁺ T cells from patients with vitiligo.

Conclusion

The present study confirmed that the cytosolic mtDNA-cGAS-STING axis of melanocytes played an important role in oxidative stress-triggered CD8⁺ T-cell response, providing novel insights into mechanisms underlying vitiligo onset.

背景：cGAS-STING轴是一种DNA传感器通路，最近已成为在多种疾病中感知应激信号和启动免疫级联的关键枢纽。然而，它在白癜风发病机制中的作用仍不清楚：探讨cGAS-STING轴在白癜风患者氧化应激和CD8+ T细胞介导的抗黑色素细胞免疫中的致病作用：方法：分别评估了氧化应激表皮细胞和白癜风周围皮肤中cGAS-STING轴和细胞膜mtDNA的表达状况。然后，我们研究了经mtDNA处理的黑色素细胞中cGAS-STING轴的激活情况，以及cGAS或STING沉默对mtDNA诱导的黑色素细胞脓毒症的影响。最后，我们还探讨了黑色素细胞热凋亡对 CD8+ T 细胞活化的旁分泌效应：我们初步证明了黑色素细胞中的 cGAS-STING 轴极易受到氧化应激的影响，并在绒毛周围皮肤的白癜风黑色素细胞中被激活，同时伴随着细胞膜 mtDNA 积累的增强。我们的体外机理实验证实，氧化应激诱导的表皮细胞线粒体损伤会导致细胞膜mtDNA积累，而mtDNA积累是激活黑色素细胞cGAS-STING轴的触发器。此外，我们还验证了细胞膜 mtDNA-cGAS-STING 轴介导了黑色素细胞的脓毒症。更重要的是，我们发现嗜热黑色素细胞产生的IL-1β和IL-18能促进白癜风患者CD8+T细胞的活化：本研究证实，黑色素细胞的细胞质mtDNA-cGAS-STING轴在氧化应激触发的CD8+ T细胞反应中发挥了重要作用，为了解白癜风的发病机制提供了新的视角。

{"title":"Cytosolic mtDNA-cGAS-STING axis mediates melanocytes pyroptosis to promote CD8+ T-cell activation in vitiligo","authors":"Xinya Xu , Xinhua Lu , Yue Zheng , Yang Xie , Wei Lai","doi":"10.1016/j.jdermsci.2024.12.002","DOIUrl":"10.1016/j.jdermsci.2024.12.002","url":null,"abstract":"<div><h3>Background</h3><div>The cGAS-STING axis, a DNA sensor pathway, has recently emerged as a key hub in sensing stress signals and initiating the immune cascade in several diseases. However, its role in the pathogenesis of vitiligo remains unclear.</div></div><div><h3>Objective</h3><div>To explore the pathogenic role of the cGAS-STING axis in linking oxidative stress and CD8<sup>+</sup> T-cell-mediated anti-melanocytic immunity in vitiligo.</div></div><div><h3>Methods</h3><div>The expression status of the cGAS-STING axis and cytosolic mtDNA were evaluated in the oxidatively stressed epidermal cells and vitiligo perilesional skin, respectively. Then, we investigated the activation of cGAS-STING axis in mtDNA-treated melanocytes, and the influence of cGAS or STING silencing on mtDNA-induced melanocytes pyroptosis. Finally, the paracrine effects of melanocytes pyroptosis on CD8<sup>+</sup> T cell activation were explored.</div></div><div><h3>Results</h3><div>We initially demonstrated that the cGAS-STING axis in melanocytes was highly susceptible to oxidative stress and activated in the vitiliginous melanocytes of perilesional skin, accompanied by enhanced cytosolic mtDNA accumulation. Our mechanistic <em>in vitro</em> experiments confirmed that oxidative stress-induced mitochondrial damage in epidermal cells led to cytosolic mtDNA accumulation, which served as a trigger in activating the cGAS-STING axis in melanocytes. Furthermore, the cytosolic mtDNA-cGAS-STING axis was verified to mediate melanocytes pyroptosis. More importantly, we found that IL-1β and IL-18 produced by pyroptotic melanocytes promoted the activation of CD8<sup>+</sup> T cells from patients with vitiligo.</div></div><div><h3>Conclusion</h3><div>The present study confirmed that the cytosolic mtDNA-cGAS-STING axis of melanocytes played an important role in oxidative stress-triggered CD8<sup>+</sup> T-cell response, providing novel insights into mechanisms underlying vitiligo onset.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"117 3","pages":"Pages 61-70"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191565","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

Unveiling intratumoral heterogeneity in high-risk cutaneous squamous cell carcinoma using single-cell spatial enhanced resolution omics-sequencing (Stereo-seq) 利用单细胞空间增强分辨率组学测序（Stereo-seq）揭示高风险皮肤鳞状细胞癌的肿瘤内异质性。

IF 4.6

Journal of dermatological science

Pub Date : 2025-03-01 DOI: 10.1016/j.jdermsci.2024.11.001

Jesse Veenstra , Ian Loveless , Peter Dimitrion , Indra Adrianto , David Ozog , Qing-Sheng Mi

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.

﹀