Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.

IF 12.6 1区医学 Q1 IMMUNOLOGY

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-05 DOI:10.1084/jem.20231512

Yingzi Cui, Qiaoni Shi, Pu Song, Jianyu Tong, Zhimin Cheng, Hangchuan Zhang, Xiaodan Wang, Yuxuan Zheng, Yao Wu, Meng Wan, Shihua Li, Xin Zhao, Zhou Tong, Zhengquan Yu, Shan Gao, Ye-Guang Chen, George Fu Gao

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引用次数: 0

Abstract

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/β-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and β-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3β inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

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柯萨奇病毒 A10 通过模拟 DKK1 来削弱 Wnt 信号，从而损害指甲再生并诱发甲沟炎。

柯萨奇病毒 A10（CV-A10）感染是儿童手足口病（HFMD）的主要病因之一，经常表现为以指甲脱落为特征的甲沟炎现象。然而，其潜在机制却难以捉摸。在这里，我们发现小鼠感染 CV-A10 后，可通过抑制 LDL 受体相关蛋白 6（LRP6）磷酸化和 β-catenin 积累来抑制 Wnt/β-catenin 信号转导，从而导致甲沟炎。从机理上讲，CV-A10可模拟Dickkopf相关蛋白1（DKK1）与CV-A10细胞受体Kringle-containing transmembrane protein 1（KRM1）相互作用。我们进一步发现，Wnt激动剂（GSK3β抑制剂）CHIR99021能恢复指甲干细胞分化，防止指甲脱落。这些发现为CV-A10及相关病毒在甲癣中的发病机制提供了新的见解，并为该病的预后评估和临床治疗提供了指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.