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http://dx.doi.org/10.5483/BMBRep.2015.48.9.140

Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail  

Kim, Joo-Hyun (Department of Bio and Fermentation Convergence Technology, Kookmin University)
Park, Seoyoung (Department of Bio and Fermentation Convergence Technology, Kookmin University)
Chung, Hyewon (Department of Opthalmology, Konkuk University School of Medicine)
Oh, Sangtaek (Department of Bio and Fermentation Convergence Technology, Kookmin University)
Publication Information
BMB Reports / v.48, no.9, 2015 , pp. 525-530 More about this Journal
Abstract
Activation of the Wnt/β-catenin pathway plays a pathogenic role in age-related macular degeneration (AMD) and is thus a potential target for the development of therapeutics for this disease. Here, we demonstrated that Wnt5a antagonized β-catenin response transcription (CRT) induced with Wnt3a by promoting β-catenin phosphorylation at Ser33/Ser37/Thr41 and its subsequent degradation in human retinal pigment epithelial (RPE) cells. Wnt5a decreased the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α(TNF-α), and nuclear factor-κB (NF-κB), which was up-regulated by Wnt3a. Furthermore, Wnt5a increased E-cadherin expression and decreased cell migration by down-regulating Snail expression, thereby abrogating the Wnt3a-induced epithelial-mesenchymal transition (EMT) in human RPE cells. Our findings suggest that Wnt5a suppresses the pathogenic effects of canonical Wnt signaling in human RPE cells by promoting β-catenin phosphorylation and degradation. Therefore, Wnt5a has significant therapeutic potential for the treatment of AMD. [BMB Reports 2015; 48(9): 525-530]
Keywords
Age-related macular degeneration; β-catenin; Canonical Wnt pathway; Retinal pigment epithelial cells; Wnt5a;
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