KY19382, a novel activator of Wnt/β-catenin signaling, promotes hair re-growth and hair follicle neogenesis

Background and Purpose: The promotion of hair regeneration and growth heavily depends on the activation of Wnt/β-catenin signaling in the hair follicle including dermal papilla (DP). KY19382, one of the newly synthesized analogs of indirubin-3’-monoxime (I3O) was identified as a Wnt/β-catenin signaling activator via inhibition of the interaction between CXXC-type zinc finger protein 5 (CXXC5) and Dishevelled (Dvl) interaction. Given the close relationship between the Wnt/β-catenin signaling and hair regeneration, we investigated the effect of KY19382 on hair re-growth and hair follicle neogenesis. Experimental Approach: In vitro hair induction effects of KY19382 was performed in human dermal papilla cells. The hair elongation effects of KY19382 was confirmed through the vibrissa culture system. In vivo hair regeneration abilities of KY19382 was identified in three models: hair regrowth, wound-induced hair follicle neogenesis (WIHN), and hair patch assays using C57BL/6 mice. The hair regeneration abilities were analyzed by immunoblotting, alkaline phosphatase (ALP) and immunohistochemical staining. Key results: KY19382 activated Wnt/β-catenin signaling and elevated the expression of ALP and proliferation marker PCNA in DP cells. KY19382 also increased hair length in ex vivo cultured mouse vibrissa follicles and induced hair regrowth in mice. Moreover, KY19382 significantly promoted the generation of de novo hair follicles as shown by WIHN and hair patch assays. Conclusion and Implications: These results indicate that KY19382 is a potential therapeutic drug that exhibits effective hair regeneration ability via activation of the Wnt/β-catenin signaling for alopecia treatments.