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Snail1 is required for the maintenance of the pancreatic acinar phenotype
The Snail1 transcriptional factor is required for correct embryonic development, yet its expression in adult animals is very limited and its functional roles are not evident. We have now conditionally inactivated Snail1 in adult mice and analyzed the phenotype of these animals. Snail1 ablation rapid...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826219/ https://www.ncbi.nlm.nih.gov/pubmed/26735179 http://dx.doi.org/10.18632/oncotarget.6785 |
_version_ | 1782426308251222016 |
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author | Loubat-Casanovas, Jordina Peña, Raúl Gonzàlez, Núria Alba-Castellón, Lorena Rosell, Santi Francí, Clara Navarro, Pilar de Herreros, Antonio García |
author_facet | Loubat-Casanovas, Jordina Peña, Raúl Gonzàlez, Núria Alba-Castellón, Lorena Rosell, Santi Francí, Clara Navarro, Pilar de Herreros, Antonio García |
author_sort | Loubat-Casanovas, Jordina |
collection | PubMed |
description | The Snail1 transcriptional factor is required for correct embryonic development, yet its expression in adult animals is very limited and its functional roles are not evident. We have now conditionally inactivated Snail1 in adult mice and analyzed the phenotype of these animals. Snail1 ablation rapidly altered pancreas structure: one month after Snail1 depletion, acinar cells were markedly depleted, and pancreas accumulated adipose tissue. Snail1 expression was not detected in the epithelium but was in pancreatic mesenchymal cells (PMCs). Snail1 ablation in cultured PMCs downregulated the expression of several β-catenin/Tcf-4 target genes, modified the secretome of these cells and decreased their ability to maintain acinar markers in cultured pancreas cells. Finally, Snail1 deficiency modified the phenotype of pancreatic tumors generated in transgenic mice expressing c-myc under the control of the elastase promoter. Specifically, Snail1 depletion did not significantly alter the size of the tumors but accelerated acinar-ductal metaplasia. These results demonstrate that Snail1 is expressed in PMCs and plays a pivotal role in maintaining acinar cells within the pancreas in normal and pathological conditions. |
format | Online Article Text |
id | pubmed-4826219 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48262192016-05-09 Snail1 is required for the maintenance of the pancreatic acinar phenotype Loubat-Casanovas, Jordina Peña, Raúl Gonzàlez, Núria Alba-Castellón, Lorena Rosell, Santi Francí, Clara Navarro, Pilar de Herreros, Antonio García Oncotarget Research Paper The Snail1 transcriptional factor is required for correct embryonic development, yet its expression in adult animals is very limited and its functional roles are not evident. We have now conditionally inactivated Snail1 in adult mice and analyzed the phenotype of these animals. Snail1 ablation rapidly altered pancreas structure: one month after Snail1 depletion, acinar cells were markedly depleted, and pancreas accumulated adipose tissue. Snail1 expression was not detected in the epithelium but was in pancreatic mesenchymal cells (PMCs). Snail1 ablation in cultured PMCs downregulated the expression of several β-catenin/Tcf-4 target genes, modified the secretome of these cells and decreased their ability to maintain acinar markers in cultured pancreas cells. Finally, Snail1 deficiency modified the phenotype of pancreatic tumors generated in transgenic mice expressing c-myc under the control of the elastase promoter. Specifically, Snail1 depletion did not significantly alter the size of the tumors but accelerated acinar-ductal metaplasia. These results demonstrate that Snail1 is expressed in PMCs and plays a pivotal role in maintaining acinar cells within the pancreas in normal and pathological conditions. Impact Journals LLC 2015-12-29 /pmc/articles/PMC4826219/ /pubmed/26735179 http://dx.doi.org/10.18632/oncotarget.6785 Text en Copyright: © 2016 Loubat-Casanovas et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Loubat-Casanovas, Jordina Peña, Raúl Gonzàlez, Núria Alba-Castellón, Lorena Rosell, Santi Francí, Clara Navarro, Pilar de Herreros, Antonio García Snail1 is required for the maintenance of the pancreatic acinar phenotype |
title | Snail1 is required for the maintenance of the pancreatic acinar phenotype |
title_full | Snail1 is required for the maintenance of the pancreatic acinar phenotype |
title_fullStr | Snail1 is required for the maintenance of the pancreatic acinar phenotype |
title_full_unstemmed | Snail1 is required for the maintenance of the pancreatic acinar phenotype |
title_short | Snail1 is required for the maintenance of the pancreatic acinar phenotype |
title_sort | snail1 is required for the maintenance of the pancreatic acinar phenotype |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826219/ https://www.ncbi.nlm.nih.gov/pubmed/26735179 http://dx.doi.org/10.18632/oncotarget.6785 |
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