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Updated: May 13, 2026

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Wnt5a attenuates Wnt/β-catenin signalling in human dermal papilla cells
Abstract:
Findings of recent studies have demonstrated modulation of Wnt/β-catenin signalling by Wnt5a, which is highly expressed in hair follicular dermal papilla (DP) in vivo. Here, we investigated the question of whether Wnt5a can affect canonical Wnt/β-catenin signalling in DP cells. Treatment with Wnt5a resulted in attenuation of Wnt3a-mediated elevation of β-catenin signalling, which was increased by Wnt5a siRNA transfection in cultured DP cells, as examined by reporter assay. In addition, treatment with Wnt5a resulted in repressed Wnt3a-mediated expression of Axin2, EP2 and LEF1 in cultured DP cells, whereas Wnt5a siRNA transfection resulted in increased Wnt3a-mediated expression of the genes in isolated DPs of cultured hair follicles. Moreover, treatment with Wnt5a resulted in attenuation of Wnt3a-mediated accumulation of β-catenin in the nucleus in DP cells. Our data strongly suggest that Wnt5a acts as an autocrine factor and attenuates canonical Wnt signalling pathway in human DP cells.
Insights
Wnt5a, highly expressed in hair dermal papilla (DP) cells, attenuates the canonical Wnt/β-catenin signaling pathway. This suggests Wnt5a acts as an autocrine factor influencing hair follicle biology.
Area of Science:
- Cell Biology
- Molecular Biology
- Dermatology
Background:
- Recent studies indicate Wnt5a modulates Wnt/β-catenin signaling, with high expression in hair follicular dermal papilla (DP) cells.
- The role of Wnt5a in regulating canonical Wnt/β-catenin signaling specifically within DP cells remains to be fully elucidated.
Discussion:
- Wnt5a treatment attenuated Wnt3a-induced β-catenin signaling and target gene expression (Axin2, EP2, LEF1) in cultured DP cells.
- Conversely, Wnt5a siRNA transfection enhanced Wnt3a-mediated signaling and gene expression in isolated DPs.
- Wnt5a inhibited Wnt3a-induced nuclear accumulation of β-catenin in DP cells.
Key Insights:
- Wnt5a functions as an autocrine factor in human DP cells.
- Wnt5a actively attenuates the canonical Wnt signaling pathway.
- This cross-talk between Wnt5a and canonical Wnt signaling is crucial for DP cell function.
Outlook:
- Further investigation into Wnt5a's precise mechanisms in DP cells could reveal therapeutic targets for hair disorders.
- Understanding this autocrine regulation may offer insights into hair follicle regeneration and homeostasis.
- Exploring the interplay between Wnt5a and other Wnt ligands could uncover novel signaling networks in hair biology.
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