The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5−/− mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5−/− mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss.
Bibliographical noteFunding Information:
We thank the Handok Pharmaceuticals for invaluable suggestions and discussion. This work was supported by grants from the National Research Foundation, the Ministry of Future Creation and Science of Korea through the Translational Research Center for Protein Function Control (2016R1A5A1004694), Mid-Career Researcher Program National Leading Research Lab (2015R1A2A1A05001873). S-HL and SHS were supported by a BK21 PLUS program. These funding sources played no role in the design of the experiments, data collection, data analysis, data interpretation, or the preparation and submission of this manuscript.
© 2017 The Authors
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology