Dickkopf-related Protein 2 Promotes Hair Growth by Upregulating the Wnt/β-catenin Signaling Pathway in Human Dermal Papilla Cells
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Background: The Wnt/β-catenin signaling pathway is crucial for the development, initiation, and growth of hair follicles (HFs). The Dickkopf-related protein (DKK) gene family encodes secreted proteins modulating the Wnt/β-catenin signaling pathway. Studies have reported that DKK1 promotes the regression of HFs and ser ves as a pathogenic mediator in male pattern bald- ness. However, the role of DKK2 on human hair growth has not yet been explored. Objective: This study investigates direct effect of DKK2 on hair growth using human dermal papilla cell (DPC) cultures and ex vivo human HF organ cultures. Methods: To elucidate the effect of DKK2 on hair growth, we examined the effect of recombinant human DKK2 (rhDKK2) treatment on cell viability, expression of mRNA and protein related to the Wnt /β-catenin signaling pathway, and cell growth in cultured human DPCs. We also performed ex vivo organ culture of HFs with rhDKK2 and measured changes in hair shaft length for 8 days. Results: Treatment with rhDKK2 led to a dose-dependent rise in the proliferation of human DPCs (p<0.05), reaching levels comparable to those induced by 1 μM minoxidil. Moreover, rhDKK2 increased the expression of Wnt/β-catenin target genes, phosphor ylated extracellular signal-regulated kinase, and cyclin-D1; it also increased the BAX-to–Bcl-2 ratio and downreg- ulated the bone morphogenetic protein 2 gene. In human HF organ cultures, relative to the control treatment, rhDKK2 treatment significantly increased hair shaft elongation (p<0.01). Conclusion: Our results indicate that rhDKK2 could promote hair growth by facilitating the proliferation of human DPCs through activation of the Wnt/β-catenin signaling pathway.
Abstract
Background: The Wnt/β-catenin signaling pathway is crucial for the development, initiation, and growth of hair follicles (HFs). The Dickkopf-related protein (DKK) gene family encodes secreted proteins modulating the Wnt/β-catenin signaling pathway. Studies have reported that DKK1 promotes the regression of HFs and ser ves as a pathogenic mediator in male pattern bald- ness. However, the role of DKK2 on human hair growth has not yet been explored. Objective: This study investigates direct effect of DKK2 on hair growth using human dermal papilla cell (DPC) cultures and ex vivo human HF organ cultures. Methods: To elucidate the effect of DKK2 on hair growth, we examined the effect of recombinant human DKK2 (rhDKK2) treatment on cell viability, expression of mRNA and protein related to the Wnt /β-catenin signaling pathway, and cell growth in cultured human DPCs. We also performed ex vivo organ culture of HFs with rhDKK2 and measured changes in hair shaft length for 8 days. Results: Treatment with rhDKK2 led to a dose-dependent rise in the proliferation of human DPCs (p<0.05), reaching levels comparable to those induced by 1 μM minoxidil. Moreover, rhDKK2 increased the expression of Wnt/β-catenin target genes, phosphor ylated extracellular signal-regulated kinase, and cyclin-D1; it also increased the BAX-to–Bcl-2 ratio and downreg- ulated the bone morphogenetic protein 2 gene. In human HF organ cultures, relative to the control treatment, rhDKK2 treatment significantly increased hair shaft elongation (p<0.01). Conclusion: Our results indicate that rhDKK2 could promote hair growth by facilitating the proliferation of human DPCs through activation of the Wnt/β-catenin signaling pathway.
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