Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.
J Exp Med
; 221(8)2024 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-38836810
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/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-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 (GSK3ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos e Proteínas de Sinalização Intercelular
/
Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade
/
Via de Sinalização Wnt
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China