PMID:23569434

Citation	Zhang, J, Li, Y, Wu, Y, Yang, T, Yang, K, Wang, R, Yang, J and Guo, H (2013) Wnt5a inhibits the proliferation and melanogenesis of melanocytes. Int J Med Sci 10:699-706
Abstract	Wnt5a, which is a noncanonical Wnt molecule, has been shown to be involved in a variety of developmental processes and cellular functions. In this study, we used "melan-a" cells as a cell model to investigate the effects of Wnt5a on melanocyte proliferation and melanogenesis, and to elucidate the possible mechanisms involved. We infected melan-a cells with recombinant Wnt5a adenoviruses to express Wnt5a protein and to simulate the Wnt5a processing environment. MTT assay and BrdU incorporation assay revealed that Wnt5a significantly inhibited the proliferation of melan-a cells. Melanin content and tyrosinase activity assays showed that Wnt5a was an inhibitor of melanin synthesis. Furthermore, RT-PCR and Western blot showed that this suppressive effect depended on noncanonical Wnt/Ror2 pathway activation and accessed the inhibition of the canonical Wnt pathway. The above results provided a novel insight into the role of Wnt5a and its related signaling in melanocyte homeostasis.
Links	PubMed PMC3619119 Online version:10.7150/ijms.5664
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:WNT5A		GO:0097325: melanocyte proliferation	ECO:0000314:		P		The results displayed in figure 1 C and D. indicate the ratio of proliferating AdWnt5a-infected cells is lower than that in control cells. This would imply that “Wnt5a inhibited the proliferation of melan-a cells.”	complete CACAO 8011
MOUSE:WNT5A		GO:0048022: negative regulation of melanin biosynthetic process	ECO:0000314:		P		Wnt5a inhibited the tyrosinase activity of melan-a cells in a dose-dependent manner compared to the control as displayed in Fig. 2A. This was confirmed by the tyrosinase activity assay results in Fig. 2B, decreased protein levels of tyrosinase and TRP1 due to Wnt5a presented in Fig. 2 C and D, and also by subcutaneous implantation experiments presented in Fig. 2 E.	complete CACAO 8021
MOUSE:WNT5A		GO:2000052: positive regulation of non-canonical Wnt receptor signaling pathway	ECO:0000314:		P		The results displayed in Fig. 3 show that Wnt5a increased the expression levels of Ror2, c-JUN, JNK1 and JNK2 in a time-dependent manner which demonstrates activation of Wnt/Ror2 signaling pathways via Wnt5a.	complete CACAO 8024
MOUSE:WNT5A		GO:0090090: negative regulation of canonical Wnt signaling pathway	ECO:0000314:		P		Both RT-PCR and Western blot analyses, found in Fig. 4 A, showed that Wnt5a significantly decreased the expression level of β-catenin in melan-a cells. Co-infection analyses displayed in Fig 4 C and D each showed that Wnt5a down-regulated the expression levels of these pigmentation-related mRNAs and proteins upregulated by Wnt3a. These results, supported by the tyrosinase activity assay in Fig 4 B, suggested that Wnt5a antagonized the canonical Wnt signaling pathway in melan-a cells.	complete CACAO 8031
MOUSE:WNT5A	involved_in	GO:0097325: melanocyte proliferation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:WNT5A	involved_in	GO:0048022: negative regulation of melanin biosynthetic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:WNT5A	involved_in	GO:2000052: positive regulation of non-canonical Wnt signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:WNT5A	involved_in	GO:0090090: negative regulation of canonical Wnt signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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