Background: When Wnt binds to the N-terminal of Frizzled, a conformational change occurs in the C-terminal of Frizzled, which binds to Dishevelled1 (Dvl1), a Wnt signaling component protein. When Dvl1 binds to the C-terminal of Frizzled, the concentration of β-catenin increases and it enters the nucleus to transmit cell proliferation signals. CXXC-type zinc finger protein 5 (CXXC5) binds to the Frizzled binding site of Dvl1 and interferes with Dvl1-Frizzled binding. Therefore, blocking CXXC5-Dvl1 binding may induce Wnt signal transduction.
Materials and methods: We used WD-aptamer, a DNA aptamer that specifically binds to Dvl1 and interferes with CXXC5-Dvl1 interaction. We confirmed the penetration of WD-aptamer into human hair follicle dermal papilla cells (HFDPCs) and measured β-catenin expression following treatment with WD-aptamer in HFDPCs, wherein Wnt signaling was activated by Wnt3a. In addition, MTT assay was performed to investigate the effect of WD-aptamer on cell proliferation.
Results: WD-aptamer penetrated the cell, affected Wnt signaling, and increased β-catenin expression, which plays an important role in signaling. Additionally, WD-aptamer induced HFDPC proliferation.
Conclusion: CXXC5-associated negative feedback of Wnt/β-catenin signaling can be regulated by interfering with CXXC5-Dvl1 interaction.
Keywords: DNA aptamer; Wnt signaling pathway; human hair follicle dermal papilla cells; proliferation; β-catenin.
© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.