DKK3-CKAP4 signaling drives fibroimmune remodeling and hair follicle miniaturization in androgenetic alopecia

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Rationale Androgenetic alopecia (AGA) is characterized by progressive hair follicle miniaturization driven by androgen signaling and alterations in the follicular microenvironment, including fibrosis and inflammation. Therefore, identifying key mediators of epithelial-mesenchymal crosstalk is essential for elucidating disease mechanisms and developing targeted therapeutic strategies. In this context, we investigated the role of the DKK3-CKAP4 signaling axis as a potential mediator of fibroimmune remodeling in AGA and evaluated its functional and therapeutic relevance. Methods We performed meta-analysis of human and mouse single-cell RNA sequencing datasets to identify candidate signaling pathways associated with AGA. Spatial expression of DKK3 and its receptor CKAP4 was validated by immunostaining. Functional roles were assessed using hair follicle organ culture and androgen-induced AGA mouse models, with pathway modulation by recombinant DKK3 and neutralizing antibodies. Single-cell transcriptomic analyses were conducted to characterize cellular and molecular changes following pathway inhibition. Results DKK3 was expressed in epithelial and mesenchymal compartments of the hair follicle, whereas CKAP4 was enriched in dermal papilla cells and dermal fibroblasts. Recombinant DKK3 suppressed hair follicle growth in organ culture, while neutralization of DKK3 or CKAP4 restored hair

Evidence level

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

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