Wnt5a attenuates Wnt/β-catenin signalling in human dermal papilla cells.

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.