Yao Lin , Yu Sun , Wenyi Hou , Xinling Chen , Feng Zhou , QingFang Xu , Yue Zheng
{"title":"FTO-mediated regulation of m6A methylation is closely related to apoptosis induced by repeated UV irradiation","authors":"Yao Lin , Yu Sun , Wenyi Hou , Xinling Chen , Feng Zhou , QingFang Xu , Yue Zheng","doi":"10.1016/j.jdermsci.2024.01.001","DOIUrl":"10.1016/j.jdermsci.2024.01.001","url":null,"abstract":"<div><h3>Background</h3><p>Ultraviolet (UV) damage is closely related to skin photoaging and many skin diseases, including dermatic tumors. N6-methyladenosine (m6A) modification is an important epigenetic regulatory mechanism. However, the role of m6A methylation in apoptosis induced by repeated UV irradiation has not been characterized.</p></div><div><h3>Objective</h3><p>To explore m6A methylation changes and regulatory mechanisms in the repeated UV-induced skin damage process, especially apoptosis.</p></div><div><h3>Methods</h3><p>HaCaT cells and BALB/c-Nu nude mice were exposed to repeated UVB/UVA+UVB irradiation. Colorimetry and flow cytometry were used to measure cellular viability and apoptosis. m6A-modified genes were detected via colorimetry and methylated RNA immunoprecipitation (MeRIP) sequencing. Methyltransferases and demethylases were detected via RT-PCR, western blotting and immunohistochemistry. Transfection of siRNA and plasmid was performed to knock down or overexpress the selected genes.</p></div><div><h3>Results</h3><p>After UVB irradiation, 861 m6A peaks were increased and 425 m6A peaks were decreased in HaCaT cells. The differentially modified genes were enriched in apoptosis-related pathways. The m6A demethylase FTO was decreased in both HaCaT cells and mouse skin after UV damage. Overexpressing FTO could improve cell viability, inhibit apoptosis and decrease RNA-m6A methylation, including LPCAT3-m6A, which increase LPCAT3 expression, cell viability promotion and apoptosis inhibition.</p></div><div><h3>Conclusion</h3><p>Our study identified the cell m6A methylation change lists after repeated UVB irradiation, and revealed that FTO and LPCAT3 play key roles in the m6A methylation pathogenesis of UV-induced skin cell apoptosis. FTO-m6A-LPCAT3 might serve as a novel upstream target for preventing and treating photoaging and UV-induced skin diseases.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 124-132"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139414762","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}
Jiaxi Chen, Yinghan Wang, Wei Dai, Xinyuan Xu, Qingrong Ni , Xiuli Yi, Pan Kang, Jingjing Ma, Lili Wu, Chunying Li, Shuli Li
{"title":"Oxidative stress-induced hypermethylation and low expression of ANXA2R: Novel insights into the dysfunction of melanocytes in vitiligo","authors":"Jiaxi Chen, Yinghan Wang, Wei Dai, Xinyuan Xu, Qingrong Ni , Xiuli Yi, Pan Kang, Jingjing Ma, Lili Wu, Chunying Li, Shuli Li","doi":"10.1016/j.jdermsci.2024.02.009","DOIUrl":"10.1016/j.jdermsci.2024.02.009","url":null,"abstract":"<div><h3>Background</h3><p>Vitiligo is a skin disorder with melanocyte destruction caused by complex interplay between multiple genetic and environmental factors. Recent studies have suggested DNA methylation is involved in the melanocyte damage, but the underlying mechanism remains unknown.</p></div><div><h3>Objective</h3><p>To explore the abnormal DNA methylation patterns in vitiligo lesional and nonlesional skin, and the mechanism of DNA methylation involved in vitiligo pathogenesis.</p></div><div><h3>Methods</h3><p>Initially, the genome-wide aberrant DNA methylation profiles in lesional and nonlesional skin of vitiligo were detect via Illumina methylation EPIC 850k Beadchip. Subsequently, a comprehensive analysis was conduct to investigate the genomic characteristics of differentially methylated regions (DMRs). Furthermore, the effects of key aberrant methylated genes on cell apoptosis and function of both melanocytes and keratinocytes were further identified and validated by western bloting, ELISA, and immunofluorescence.</p></div><div><h3>Results</h3><p>Compared with nonlesional skins, we discovered 79 significantly differentially methylated CpG sites in vitiligo lesions. These DMRs were mainly located in the gene body and the TS1500 region. Annexin A2 receptor (ANXA2R), a crucial gene in cell apoptosis, was hypermethylated in vitiligo lesions. Furthermore, we showed that ANXA2R displayed hypermethylation and low expression levels in both keratinocytes and melanocytes of vitiligo patients, and the hypermethylated-triggered downregulation of ANXA2R under oxidative stress induced melanocyte apoptosis, and inhibited the secretion of stem cell factor (SCF) from keratinocytes thus impaired the survival of melanocytes.</p></div><div><h3>Conclusions</h3><p>Our study illustrates the DNA methylation modification in vitiligo, and further demonstrates the molecular mechanism of hypermethylated ANXA2R in the dysfunction of melanocytes under oxidative stress.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 115-123"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140469638","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}
Tam Kurachi, Hironobu Ishimaru, Ryo Tadakuma, Miu Okaue, Akira Koda, Yuhki Ueda, Takaaki Doi
{"title":"Mucopolysaccharide polysulfate increases local skin blood volume through nitric oxide production","authors":"Tam Kurachi, Hironobu Ishimaru, Ryo Tadakuma, Miu Okaue, Akira Koda, Yuhki Ueda, Takaaki Doi","doi":"10.1016/j.jdermsci.2024.05.001","DOIUrl":"10.1016/j.jdermsci.2024.05.001","url":null,"abstract":"<div><h3>Background</h3><p>Mucopolysaccharide polysulfate (MPS) is widely used as an active ingredient in topical preparations for the treatment of asteatosis and blood flow disorders. Although topical MPS products can increase cutaneous blood flow (CBF), the underlying mechanism remains unclear.</p></div><div><h3>Objective</h3><p>In this study, we aimed to elucidate how MPS increases CBF. We investigated the association of nitric oxide (NO), a powerful mediator associated with increased local blood volume, with the blood flow-accelerating action of MPS in mice. In addition, we verified the effects of MPS on NO production in different skin cell types, such as keratinocytes (KCs), endothelial cells (ECs), and dermal fibroblasts (DFs).</p></div><div><h3>Methods</h3><p>We used raster-scanning optoacoustic imaging mesoscopy to observe <em>in vivo</em> changes in the skin blood volume. NO production was determined in each cell using an NO indicator. An enzyme-linked immunoassay was used to measure the phosphorylated nitric oxide synthase (NOS) levels in ECs, DFs, and KCs in the presence or absence of MPS.</p></div><div><h3>Results</h3><p>Topical application of MPS increased the skin blood volume in mice, and this increase was abolished through the addition of NOS inhibitors. MPS promoted the dose-dependent production of NO in various cells, which caused alterations in the phosphorylation state of NOS.</p></div><div><h3>Conclusion</h3><p>Our findings demonstrate that MPS promotes an increase in skin blood volume and NO production in various skin cell types. These results suggest that MPS can potentially accelerate CBF through the NO biosynthesis pathway in different skin cell types.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 3","pages":"Pages 133-140"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000823/pdfft?md5=89e4a267488d198e2a9471e26233865b&pid=1-s2.0-S0923181124000823-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141029937","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}
Shirin Emtenani , Beke E. Linnemann , Andreas Recke , Anabelle von Georg , Stephanie Goletz , Enno Schmidt , Nina van Beek
{"title":"Anti-BP230 IgE autoantibodies in bullous pemphigoid intraindividually correlate with disease activity","authors":"Shirin Emtenani , Beke E. Linnemann , Andreas Recke , Anabelle von Georg , Stephanie Goletz , Enno Schmidt , Nina van Beek","doi":"10.1016/j.jdermsci.2024.03.009","DOIUrl":"10.1016/j.jdermsci.2024.03.009","url":null,"abstract":"<div><h3>Background</h3><p>Bullous pemphigoid (BP), the most common subepidermal autoimmune blistering disease, is classically defined by the presence of IgG autoantibodies directed against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230 and the predominance of skin lesions. Several studies have addressed the role of anti-BP180 IgE in patients and experimental models, while data on anti-BP230 IgE are scarce.</p></div><div><h3>Objective</h3><p>To assess anti-BP230 IgE level by ELISA in BP sera and to correlate it with disease severity and clinical characteristics.</p></div><div><h3>Methods</h3><p>BP sera underwent anti-BP230 IgE ELISA and Western blotting against human BP230 fragments.</p></div><div><h3>Results</h3><p>We demonstrate that 36/154 (23%) of BP sera were positive for anti-BP230 IgE. Anti-BP230 IgE levels had no correlation with clinical phenotype or disease activity per se. Interestingly, anti-BP230 IgE was significantly associated with disease activity within individuals during the course of the disease. Additionally, anti-BP230 IgE and total IgE levels showed a significant correlation. Notably, anti-BP230 IgG correlated interindividually with disease activity. By Western blotting, the C-terminal domain of BP230 fragments (C2; amino acids 2024–2349 and C3; amino acids 2326–2649), provided the best serological assay for anti-BP230 IgE detection.</p></div><div><h3>Conclusion</h3><p>As a complementary tool, IgE immunoblotting is recommended to obtain an optimal serological diagnosis, particularly in patients with severe disease without IgG reactivity by BP180- or BP230-specific ELISA. Although the detection of serum anti-BP230 IgE is not of major diagnostic significance, it may be relevant for therapeutic decisions, e.g., for anti-IgE-directed treatment, which has been successfully used in case series of BP.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 2","pages":"Pages 64-70"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000550/pdfft?md5=44c4ae5d075f19f0b790f0f27c49e88c&pid=1-s2.0-S0923181124000550-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271196","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}
Takeshi Fukumoto , Tomoka Harada , Takamichi Ito , Satoshi Fukushima , Ryusuke Ono , Masutaka Furue , Chikako Nishigori
{"title":"DNA repair ability in a patient with voriconazole-related squamous cell carcinoma that required differential diagnosis from xeroderma pigmentosum","authors":"Takeshi Fukumoto , Tomoka Harada , Takamichi Ito , Satoshi Fukushima , Ryusuke Ono , Masutaka Furue , Chikako Nishigori","doi":"10.1016/j.jdermsci.2024.02.005","DOIUrl":"10.1016/j.jdermsci.2024.02.005","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 2","pages":"Pages 83-85"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140804429","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":"Visualization of intradermal blood vessel structures by dual-wavelength photoacoustic microscopy and characterization of three-dimensional construction of livedo-racemosa in cutaneous polyarteritis nodosa","authors":"Kazuyo Sujino , Keiji Tanese , Yasuko Saito , Junko Kuramoto , Hideaki Iwazaki , Taiichiro Ida , Sadakazu Aiso , Nobuaki Imanishi , Hiroki Kajita , Keitaro Fukuda , Masayuki Amagai , Akiko Tanikawa","doi":"10.1016/j.jdermsci.2024.03.010","DOIUrl":"10.1016/j.jdermsci.2024.03.010","url":null,"abstract":"<div><h3>Background</h3><p>Photoacoustic microscopy is expected to have clinical applications as a noninvasive and three-dimensional (3D) method of observing intradermal structures.</p></div><div><h3>Objective</h3><p>Investigate the applicability of a photoacoustic microscope equipped with two types of pulsed lasers that can simultaneously recognize hemoglobin and melanin.</p></div><div><h3>Methods</h3><p>16 skin lesions including erythema, pigmented lesions, vitiligo and purpura, were analyzed to visualize 3D structure of melanin granule distribution and dermal blood vessels. 13 cases of livedo racemosa in cutaneous polyarteritis nodosa (cPN) were further analyzed to visualize the 3D structure of dermal blood vessels in detail. Vascular structure was also analyzed in the biopsy specimens obtained from tender indurated erythema of cPN by CD34 immunostaining.</p></div><div><h3>Results</h3><p>Hemoglobin-recognition signal clearly visualized the 3D structure of dermal blood vessels and melanin-recognition signal was consistently reduced in vitiligo. In livedo racemosa, the hemoglobin-recognition signal revealed a relatively thick and large reticular structure in the deeper layers that became denser and finer toward the upper layers. The numerical analysis revealed that the number of dermal blood vessels was 1.29-fold higher (p<0.05) in the deeper region of the lesion than that of normal skin. The CD34 immunohistochemical analysis in tender indurated erythema revealed an increased number of dermal vessels compared with normal skin in 88.9% (8/9) of the cases, suggesting that vascular network remodeling had occurred in cPN.</p></div><div><h3>Conclusion</h3><p>The photoacoustic system has an advantage in noninvasively detecting dermal blood vessel structures that are difficult to recognize by two-dimensional histopathology specimen examination and is worth evaluating in various skin diseases.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"114 2","pages":"Pages 71-78"},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000562/pdfft?md5=7d7bfd13601c7ef9c5cc256f9d4d7104&pid=1-s2.0-S0923181124000562-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140405902","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}