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

Exp Dermatol. 2013 Mar;22(3):229-31. doi: 10.1111/exd.12101.
Wnt5a attenuates Wnt/β-catenin signalling in human dermal papilla cells.
Kwack MH, Kim MK, Kim JC, Sung YK.

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.

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Acta Physiol (Oxf). 2012 Jan;204(1):17-33. doi: 10.1111/j.1748-1716.2011.02294.x. Epub 2011 Apr 22.
Wnt5a: its signalling, functions and implication in diseases.
Kikuchi A, Yamamoto H, Sato A, Matsumoto S.

Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan. akikuchi@molbiobc.med.osaka-u.ac.jp

Wnt5a is a representative ligand that activates the β-catenin-independent pathways. Because the β-catenin-independent pathway includes multiple signalling cascades in addition to the planar cell polarity and Ca(2+) pathway, Wnt5a regulates a variety of cellular functions, such as proliferation, differentiation, migration, adhesion and polarity. Consistent with the multiple functions of Wnt5a signalling, Wnt5a knockout mice show various phenotypes, including an inability to extend the embryonic anterior-posterior and proximal-distal axes in outgrowth tissues. Thus, many important roles of Wnt5a in developmental processes have been demonstrated. Moreover, recent reports suggest that the postnatal abnormalities in the Wnt5a signalling are involved in various diseases, such as cancer, inflammatory diseases and metabolic disorders. Therefore, Wnt5a and its signalling pathways could be important targets for the diagnosis and therapy for human diseases.