Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782384138971512832 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4523936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kechenyeh irf6isthemediatoroftgfb3duringregulationoftheepithelialmesenchymaltransitionandpalatalfusion AT xiaowenlin irf6isthemediatoroftgfb3duringregulationoftheepithelialmesenchymaltransitionandpalatalfusion AT chenchunming irf6isthemediatoroftgfb3duringregulationoftheepithelialmesenchymaltransitionandpalatalfusion AT lolunjou irf6isthemediatoroftgfb3duringregulationoftheepithelialmesenchymaltransitionandpalatalfusion AT wongfenhwa irf6isthemediatoroftgfb3duringregulationoftheepithelialmesenchymaltransitionandpalatalfusion |