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IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion

Mutation in interferon regulatory factor 6 (IRF6) is known to cause syndromic and non-syndromic cleft lip/palate in human. In this study, we investigated the molecular mechanisms related to IRF6 during palatal fusion using palatal shelves organ culture. The results showed that ablation of Irf6 resul...

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Autores principales: Ke, Chen-Yeh, Xiao, Wen-Lin, Chen, Chun-Ming, Lo, Lun-Jou, Wong, Fen-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523936/
https://www.ncbi.nlm.nih.gov/pubmed/26240017
http://dx.doi.org/10.1038/srep12791
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author Ke, Chen-Yeh
Xiao, Wen-Lin
Chen, Chun-Ming
Lo, Lun-Jou
Wong, Fen-Hwa
author_facet Ke, Chen-Yeh
Xiao, Wen-Lin
Chen, Chun-Ming
Lo, Lun-Jou
Wong, Fen-Hwa
author_sort Ke, Chen-Yeh
collection PubMed
description Mutation in interferon regulatory factor 6 (IRF6) is known to cause syndromic and non-syndromic cleft lip/palate in human. In this study, we investigated the molecular mechanisms related to IRF6 during palatal fusion using palatal shelves organ culture. The results showed that ablation of Irf6 resulted in a delay in TGFβ3-regulated palatal fusion. Ectopic expression of IRF6 was able to promote palatal fusion and rescue shTgfβ3-induced fusion defect. These findings indicate that IRF6 is involved in TGFβ3-mediated palatal fusion. Molecular analysis revealed that ectopic expression of IRF6 increased the expression of SNAI2, an epithelial mesenchymal transition (EMT) regulator, and diminished the expression of various epithelial markers, such as E-cadherin, Plakophilin and ZO-1. In addition, knockdown of Irf6 expression decreased SNAI2 expression, and restored the expression of ZO-1 and Plakophilin that were diminished by TGFβ3. Blocking of Snai2 expression delayed palatal fusion and abolished the IRF6 rescuing effect associated with shTgfβ3-induced fusion defect. These findings indicate that TGFβ3 increases IRF6 expression and subsequently regulates SNAI2 expression, and IRF6 appears to regulate EMT during palatal fusion via SNAI2. Taken together, this study demonstrates that IRF6 is a mediator of TGFβ3, which regulates EMT and fusion process during the embryonic palate development.
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spelling pubmed-45239362015-08-05 IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion Ke, Chen-Yeh Xiao, Wen-Lin Chen, Chun-Ming Lo, Lun-Jou Wong, Fen-Hwa Sci Rep Article Mutation in interferon regulatory factor 6 (IRF6) is known to cause syndromic and non-syndromic cleft lip/palate in human. In this study, we investigated the molecular mechanisms related to IRF6 during palatal fusion using palatal shelves organ culture. The results showed that ablation of Irf6 resulted in a delay in TGFβ3-regulated palatal fusion. Ectopic expression of IRF6 was able to promote palatal fusion and rescue shTgfβ3-induced fusion defect. These findings indicate that IRF6 is involved in TGFβ3-mediated palatal fusion. Molecular analysis revealed that ectopic expression of IRF6 increased the expression of SNAI2, an epithelial mesenchymal transition (EMT) regulator, and diminished the expression of various epithelial markers, such as E-cadherin, Plakophilin and ZO-1. In addition, knockdown of Irf6 expression decreased SNAI2 expression, and restored the expression of ZO-1 and Plakophilin that were diminished by TGFβ3. Blocking of Snai2 expression delayed palatal fusion and abolished the IRF6 rescuing effect associated with shTgfβ3-induced fusion defect. These findings indicate that TGFβ3 increases IRF6 expression and subsequently regulates SNAI2 expression, and IRF6 appears to regulate EMT during palatal fusion via SNAI2. Taken together, this study demonstrates that IRF6 is a mediator of TGFβ3, which regulates EMT and fusion process during the embryonic palate development. Nature Publishing Group 2015-08-04 /pmc/articles/PMC4523936/ /pubmed/26240017 http://dx.doi.org/10.1038/srep12791 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ke, Chen-Yeh
Xiao, Wen-Lin
Chen, Chun-Ming
Lo, Lun-Jou
Wong, Fen-Hwa
IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion
title IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion
title_full IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion
title_fullStr IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion
title_full_unstemmed IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion
title_short IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion
title_sort irf6 is the mediator of tgfβ3 during regulation of the epithelial mesenchymal transition and palatal fusion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523936/
https://www.ncbi.nlm.nih.gov/pubmed/26240017
http://dx.doi.org/10.1038/srep12791
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