{"title":"天疱疮热下垂的新见解:从细胞结构到治疗靶向。","authors":"Jiazhen Chen, Zezhi He, Xiangnong Dai, Sifan Lin, Jiahui Liu, Xingdong Ye","doi":"10.1016/j.abd.2024.07.015","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pemphigus is an autoimmune blistering disease where autoantibodies target desmoglein (Dsg) antigens on keratinocytes, triggering the p38 MAPK pathway, Dsg internalization, desmosomal dissolution, and keratinocyte apoptosis, are essential for blister formation. Recent research indicates keratinocyte pyroptosis may exacerbate acantholysis and delay wound healing. Current treatments, including corticosteroids and immunosuppressants, are effective but have significant side effects, such as prolonged wound healing and increased infection risk. Understanding these inflammatory processes is crucial for developing effective treatments for pemphigus.</p><p><strong>Methods: </strong>The authors conducted a comprehensive review of the literature, analyzing recent findings regarding the upregulation of pyroptosis-related proteins in pemphigus.</p><p><strong>Results: </strong>The present findings highlight a significant upregulation of pyroptosis-related proteins, which play a crucial role in the inflammatory response and blister formation characteristic of pemphigus. Key proteins such as cytokines IL-1β, IL-18, High Mobility Group Box-1 (HMGB1), and Parkin, along with NOD-like receptors and P2×7 receptors, were identified as pivotal in facilitating pyroptosis. The study also discusses potential therapeutic approaches targeting these proteins to modulate the disease pathway effectively.</p><p><strong>Study limitations: </strong>This study aimed to investigate the role of pyroptosis in the pathogenesis of pemphigus, focusing on its potential as a novel therapeutic target.</p><p><strong>Conclusions: </strong>Pyroptosis significantly contributes to the pathogenesis of pemphigus and presents a promising target for therapy. Targeting specific molecules involved in the pyroptosis pathway offers the potential for developing more precise and less toxic treatments, allowing the shift from traditional therapies towards targeted therapeutic strategies.</p>","PeriodicalId":7787,"journal":{"name":"Anais brasileiros de dermatologia","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"New insights into pyroptosis in pemphigus: from cellular structure to therapeutic targeting.\",\"authors\":\"Jiazhen Chen, Zezhi He, Xiangnong Dai, Sifan Lin, Jiahui Liu, Xingdong Ye\",\"doi\":\"10.1016/j.abd.2024.07.015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pemphigus is an autoimmune blistering disease where autoantibodies target desmoglein (Dsg) antigens on keratinocytes, triggering the p38 MAPK pathway, Dsg internalization, desmosomal dissolution, and keratinocyte apoptosis, are essential for blister formation. Recent research indicates keratinocyte pyroptosis may exacerbate acantholysis and delay wound healing. Current treatments, including corticosteroids and immunosuppressants, are effective but have significant side effects, such as prolonged wound healing and increased infection risk. Understanding these inflammatory processes is crucial for developing effective treatments for pemphigus.</p><p><strong>Methods: </strong>The authors conducted a comprehensive review of the literature, analyzing recent findings regarding the upregulation of pyroptosis-related proteins in pemphigus.</p><p><strong>Results: </strong>The present findings highlight a significant upregulation of pyroptosis-related proteins, which play a crucial role in the inflammatory response and blister formation characteristic of pemphigus. Key proteins such as cytokines IL-1β, IL-18, High Mobility Group Box-1 (HMGB1), and Parkin, along with NOD-like receptors and P2×7 receptors, were identified as pivotal in facilitating pyroptosis. The study also discusses potential therapeutic approaches targeting these proteins to modulate the disease pathway effectively.</p><p><strong>Study limitations: </strong>This study aimed to investigate the role of pyroptosis in the pathogenesis of pemphigus, focusing on its potential as a novel therapeutic target.</p><p><strong>Conclusions: </strong>Pyroptosis significantly contributes to the pathogenesis of pemphigus and presents a promising target for therapy. 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引用次数: 0
摘要
背景:天疱疮是一种自身免疫性水疱疾病,其自身抗体靶向角化细胞上的桥粒蛋白(Dsg)抗原,触发p38 MAPK通路,Dsg内化,桥粒溶解和角化细胞凋亡,是水疱形成所必需的。最近的研究表明,角化细胞焦亡可能加剧棘层溶解和延迟伤口愈合。目前的治疗方法,包括皮质类固醇和免疫抑制剂,是有效的,但有明显的副作用,如延长伤口愈合和增加感染风险。了解这些炎症过程对于开发有效的天疱疮治疗方法至关重要。方法:作者对文献进行了全面的回顾,分析了天疱疮中有关热中毒相关蛋白上调的最新发现。结果:目前的研究结果表明,在天疱疮的炎症反应和水疱形成特征中起关键作用的热裂解相关蛋白显著上调。关键蛋白如细胞因子IL-1β、IL-18、High Mobility Group Box-1 (HMGB1)和Parkin,以及nod样受体和P2×7受体,被认为是促进焦亡的关键。该研究还讨论了针对这些蛋白质有效调节疾病途径的潜在治疗方法。研究局限性:本研究旨在探讨热下垂在天疱疮发病机制中的作用,重点关注其作为一种新的治疗靶点的潜力。结论:热下垂在天疱疮的发病机制中起着重要作用,是一个有希望的治疗靶点。针对参与焦亡途径的特定分子提供了开发更精确和更低毒性治疗的潜力,允许从传统治疗向靶向治疗策略的转变。
New insights into pyroptosis in pemphigus: from cellular structure to therapeutic targeting.
Background: Pemphigus is an autoimmune blistering disease where autoantibodies target desmoglein (Dsg) antigens on keratinocytes, triggering the p38 MAPK pathway, Dsg internalization, desmosomal dissolution, and keratinocyte apoptosis, are essential for blister formation. Recent research indicates keratinocyte pyroptosis may exacerbate acantholysis and delay wound healing. Current treatments, including corticosteroids and immunosuppressants, are effective but have significant side effects, such as prolonged wound healing and increased infection risk. Understanding these inflammatory processes is crucial for developing effective treatments for pemphigus.
Methods: The authors conducted a comprehensive review of the literature, analyzing recent findings regarding the upregulation of pyroptosis-related proteins in pemphigus.
Results: The present findings highlight a significant upregulation of pyroptosis-related proteins, which play a crucial role in the inflammatory response and blister formation characteristic of pemphigus. Key proteins such as cytokines IL-1β, IL-18, High Mobility Group Box-1 (HMGB1), and Parkin, along with NOD-like receptors and P2×7 receptors, were identified as pivotal in facilitating pyroptosis. The study also discusses potential therapeutic approaches targeting these proteins to modulate the disease pathway effectively.
Study limitations: This study aimed to investigate the role of pyroptosis in the pathogenesis of pemphigus, focusing on its potential as a novel therapeutic target.
Conclusions: Pyroptosis significantly contributes to the pathogenesis of pemphigus and presents a promising target for therapy. Targeting specific molecules involved in the pyroptosis pathway offers the potential for developing more precise and less toxic treatments, allowing the shift from traditional therapies towards targeted therapeutic strategies.
期刊介绍:
The journal is published bimonthly and is devoted to the dissemination of original, unpublished technical-scientific study, resulting from research or reviews of dermatological topics and related matters. Exchanges with other publications may be accepted.