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Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development

Cadherin-mediated cell-cell adhesion plays an important role in organ development and changes in cadherin expression are often linked to morphogenetic and pathogenic events. Cadherins interact with other intracellular components to form adherens junctions (AJs) and provide mechanical attachments bet...

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Autores principales: Serrill, Jeffrey D., Sander, Maike, Shih, Hung Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128895/
https://www.ncbi.nlm.nih.gov/pubmed/30194315
http://dx.doi.org/10.1038/s41598-018-31603-2
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author Serrill, Jeffrey D.
Sander, Maike
Shih, Hung Ping
author_facet Serrill, Jeffrey D.
Sander, Maike
Shih, Hung Ping
author_sort Serrill, Jeffrey D.
collection PubMed
description Cadherin-mediated cell-cell adhesion plays an important role in organ development and changes in cadherin expression are often linked to morphogenetic and pathogenic events. Cadherins interact with other intracellular components to form adherens junctions (AJs) and provide mechanical attachments between adjacent cells. E-cadherin (Cdh1) represents an integral component of these intercellular junctions. To elucidate the function of E-cadherin in the developing pancreas, we generated and studied pancreas-specific Cdh1-knockout (Cdh1(ΔPan/ΔPan)) mice. Cdh1(ΔPan/ΔPan) mice exhibit normal body size at birth, but fail to gain weight and become hypoglycemic soon afterward. We found that E-cadherin is not required for the establishment of apical-basal polarity or pancreatic exocrine cell identity at birth. However, four days after birth, the pancreata of Cdh1(ΔPan/ΔPan) mutants display progressive deterioration of exocrine architecture and dysregulation of Wnt and YAP signaling. At this time point, the acinar cells of Cdh1(ΔPan/ΔPan) mutants begin to exhibit ductal phenotypes, suggesting acinar-to-ductal metaplasia (ADM) in the E-cadherin-deficient pancreas. Our findings demonstrate that E-cadherin plays an integral role in the maintenance of exocrine architecture and regulation of homeostatic signaling. The present study provides insights into the involvement of cadherin-mediated cell-cell adhesion in pathogenic conditions such as pancreatitis or pancreatic cancer.
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spelling pubmed-61288952018-09-10 Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development Serrill, Jeffrey D. Sander, Maike Shih, Hung Ping Sci Rep Article Cadherin-mediated cell-cell adhesion plays an important role in organ development and changes in cadherin expression are often linked to morphogenetic and pathogenic events. Cadherins interact with other intracellular components to form adherens junctions (AJs) and provide mechanical attachments between adjacent cells. E-cadherin (Cdh1) represents an integral component of these intercellular junctions. To elucidate the function of E-cadherin in the developing pancreas, we generated and studied pancreas-specific Cdh1-knockout (Cdh1(ΔPan/ΔPan)) mice. Cdh1(ΔPan/ΔPan) mice exhibit normal body size at birth, but fail to gain weight and become hypoglycemic soon afterward. We found that E-cadherin is not required for the establishment of apical-basal polarity or pancreatic exocrine cell identity at birth. However, four days after birth, the pancreata of Cdh1(ΔPan/ΔPan) mutants display progressive deterioration of exocrine architecture and dysregulation of Wnt and YAP signaling. At this time point, the acinar cells of Cdh1(ΔPan/ΔPan) mutants begin to exhibit ductal phenotypes, suggesting acinar-to-ductal metaplasia (ADM) in the E-cadherin-deficient pancreas. Our findings demonstrate that E-cadherin plays an integral role in the maintenance of exocrine architecture and regulation of homeostatic signaling. The present study provides insights into the involvement of cadherin-mediated cell-cell adhesion in pathogenic conditions such as pancreatitis or pancreatic cancer. Nature Publishing Group UK 2018-09-07 /pmc/articles/PMC6128895/ /pubmed/30194315 http://dx.doi.org/10.1038/s41598-018-31603-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Serrill, Jeffrey D.
Sander, Maike
Shih, Hung Ping
Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development
title Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development
title_full Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development
title_fullStr Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development
title_full_unstemmed Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development
title_short Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E-cadherin During Postnatal Development
title_sort pancreatic exocrine tissue architecture and integrity are maintained by e-cadherin during postnatal development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128895/
https://www.ncbi.nlm.nih.gov/pubmed/30194315
http://dx.doi.org/10.1038/s41598-018-31603-2
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