Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling

The study investigates the role of Pyruvate Kinase M2 (PKM2), a key enzyme in glycolysis, in hair growth and its relationship with Wnt/β-catenin signaling, which is involved in hair regeneration. The research was conducted using depilation-induced anagen progression and wound-induced hair follicle neogenesis in C57BL/6 mice. The results showed that the expression and activity of PKM2 increased during anagen progression. The study also found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of hair follicle stem cells (HFSCs). PKM2 expression was increased via up-regulation of the Wnt/β-catenin signaling. Furthermore, a combined treatment with KY19382, a small molecule that activates the Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth. The findings suggest that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.