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Researchers Uncover Mechanism Behind Nail Shedding Related to Hand-Foot-and-Mouth Disease

Jun 11, 2024

Hand-foot-and-mouth disease (HFMD) is a prevalent viral infection among children, often causing sores in the mouth and a rash on the hands and feet. 

Onychomadesis (nail shedding) is a common post-HFMD pathological phenomenon. Until now, the mechanisms driving this sequela have been poorly understood, making prevention and treatment of post-HFMD onychomadesis challenging.  

In a study published in Journal of Experimental Medicine, the research group led by Prof. George Fu Gao (GAO Fu) from the Institute of Microbiology of the Chinese Academy of Sciences, and the collaborators from Tsinghua University and Southeast Universityuncovered the connection between virus-receptor interaction and pathologic phenomenon through the modulation of cell signaling, and the establishment of links between virus infection and post-HFMD onychomadesis.

Based on previous structural studies, researchers found that Coxsackievirus A10 (CV-A10, a prominent pathogenic virus of HFMD) infection, mimics the action of a known regulatory protein, Dickkopf-related protein 1 (DKK1), which is crucial in managing Wnt/β-catenin signaling involved in nail growth.  

They found that by mimicking DKK1, CV-A10 binds to its receptor KREMEN1 and interferes with the Wnt/β-catenin signaling pathway by inhibiting LRP6 phosphorylation and β-catenin accumulation. This interference leads to dysfunction of cell proliferation and nail stem cell differentiation, which consequently manifests as onychomadesis.  

Importantly, researchers provided convincing evidence that activation of Wnt signaling with the small molecule CHIR99021 could rescue nail stem cell differentiation in digit tips, and holds promising potential as an effective treatment for onychomadesis. 

This study highlights the activation of the Wnt pathway as a potential treatment, and offers new insights into virus-host cellular signaling interactions. 

Contact

George Fu Gao

Institute of Microbiology

E-mail:

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

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