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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 |
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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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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
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 | ||||
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 | ||||
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 | ||||
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 | ||||
involved_in |
GO:0097325: melanocyte proliferation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0048022: negative regulation of melanin biosynthetic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
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 | |||
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 | |||
See also
References
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