Cargando…

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

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 pro...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Joo-Hyun, Park, Seoyoung, Chung, Hyewon, Oh, Sangtaek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641237/
https://www.ncbi.nlm.nih.gov/pubmed/26246285
http://dx.doi.org/10.5483/BMBRep.2015.48.9.140
_version_ 1782400165123981312
author Kim, Joo-Hyun
Park, Seoyoung
Chung, Hyewon
Oh, Sangtaek
author_facet Kim, Joo-Hyun
Park, Seoyoung
Chung, Hyewon
Oh, Sangtaek
author_sort Kim, Joo-Hyun
collection PubMed
description 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]
format Online
Article
Text
id pubmed-4641237
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Korean Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-46412372015-11-16 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 Park, Seoyoung Chung, Hyewon Oh, Sangtaek BMB Rep Research Article 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] Korean Society for Biochemistry and Molecular Biology 2015-09 /pmc/articles/PMC4641237/ /pubmed/26246285 http://dx.doi.org/10.5483/BMBRep.2015.48.9.140 Text en Copyright © 2015, Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kim, Joo-Hyun
Park, Seoyoung
Chung, Hyewon
Oh, Sangtaek
Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail
title Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail
title_full Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail
title_fullStr Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail
title_full_unstemmed Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail
title_short Wnt5a attenuates the pathogenic effects of the Wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and Snail
title_sort wnt5a attenuates the pathogenic effects of the wnt/β-catenin pathway in human retinal pigment epithelial cells via down-regulating β-catenin and snail
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641237/
https://www.ncbi.nlm.nih.gov/pubmed/26246285
http://dx.doi.org/10.5483/BMBRep.2015.48.9.140
work_keys_str_mv AT kimjoohyun wnt5aattenuatesthepathogeniceffectsofthewntbcateninpathwayinhumanretinalpigmentepithelialcellsviadownregulatingbcateninandsnail
AT parkseoyoung wnt5aattenuatesthepathogeniceffectsofthewntbcateninpathwayinhumanretinalpigmentepithelialcellsviadownregulatingbcateninandsnail
AT chunghyewon wnt5aattenuatesthepathogeniceffectsofthewntbcateninpathwayinhumanretinalpigmentepithelialcellsviadownregulatingbcateninandsnail
AT ohsangtaek wnt5aattenuatesthepathogeniceffectsofthewntbcateninpathwayinhumanretinalpigmentepithelialcellsviadownregulatingbcateninandsnail