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Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine
Loss of integrity of the epithelial/mucosal barrier in the small intestine has been associated with different pathologies that originate and/or develop in the gastrointestinal tract. We showed recently that mucin, the main protein in the mucus layer, is disrupted during early periods of intestinal i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387149/ https://www.ncbi.nlm.nih.gov/pubmed/22768227 http://dx.doi.org/10.1371/journal.pone.0040087 |
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author | Chang, Marisol Alsaigh, Tom Kistler, Erik B. Schmid-Schönbein, Geert W. |
author_facet | Chang, Marisol Alsaigh, Tom Kistler, Erik B. Schmid-Schönbein, Geert W. |
author_sort | Chang, Marisol |
collection | PubMed |
description | Loss of integrity of the epithelial/mucosal barrier in the small intestine has been associated with different pathologies that originate and/or develop in the gastrointestinal tract. We showed recently that mucin, the main protein in the mucus layer, is disrupted during early periods of intestinal ischemia. This event is accompanied by entry of pancreatic digestive enzymes into the intestinal wall. We hypothesize that the mucin-containing mucus layer is the main barrier preventing digestive enzymes from contacting the epithelium. Mucin breakdown may render the epithelium accessible to pancreatic enzymes, causing its disruption and increased permeability. The objective of this study was to investigate the role of mucin as a protection for epithelial integrity and function. A rat model of 30 min splanchnic arterial occlusion (SAO) was used to study the degradation of two mucin isoforms (mucin 2 and 13) and two epithelial membrane proteins (E-cadherin and toll-like receptor 4, TLR4). In addition, the role of digestive enzymes in mucin breakdown was assessed in this model by luminal inhibition with acarbose, tranexamic acid, or nafamostat mesilate. Furthermore, the protective effect of the mucin layer against trypsin-mediated disruption of the intestinal epithelium was studied in vitro. Rats after SAO showed degradation of mucin 2 and fragmentation of mucin 13, which was not prevented by protease inhibition. Mucin breakdown was accompanied by increased intestinal permeability to FITC-dextran as well as degradation of E-cadherin and TLR4. Addition of mucin to intestinal epithelial cells in vitro protected against trypsin-mediated degradation of E-cadherin and TLR4 and reduced permeability of FITC-dextran across the monolayer. These results indicate that mucin plays an important role in the preservation of the mucosal barrier and that ischemia but not digestive enzymes disturbs mucin integrity, while digestive enzymes actively mediate epithelial cell disruption. |
format | Online Article Text |
id | pubmed-3387149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33871492012-07-05 Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine Chang, Marisol Alsaigh, Tom Kistler, Erik B. Schmid-Schönbein, Geert W. PLoS One Research Article Loss of integrity of the epithelial/mucosal barrier in the small intestine has been associated with different pathologies that originate and/or develop in the gastrointestinal tract. We showed recently that mucin, the main protein in the mucus layer, is disrupted during early periods of intestinal ischemia. This event is accompanied by entry of pancreatic digestive enzymes into the intestinal wall. We hypothesize that the mucin-containing mucus layer is the main barrier preventing digestive enzymes from contacting the epithelium. Mucin breakdown may render the epithelium accessible to pancreatic enzymes, causing its disruption and increased permeability. The objective of this study was to investigate the role of mucin as a protection for epithelial integrity and function. A rat model of 30 min splanchnic arterial occlusion (SAO) was used to study the degradation of two mucin isoforms (mucin 2 and 13) and two epithelial membrane proteins (E-cadherin and toll-like receptor 4, TLR4). In addition, the role of digestive enzymes in mucin breakdown was assessed in this model by luminal inhibition with acarbose, tranexamic acid, or nafamostat mesilate. Furthermore, the protective effect of the mucin layer against trypsin-mediated disruption of the intestinal epithelium was studied in vitro. Rats after SAO showed degradation of mucin 2 and fragmentation of mucin 13, which was not prevented by protease inhibition. Mucin breakdown was accompanied by increased intestinal permeability to FITC-dextran as well as degradation of E-cadherin and TLR4. Addition of mucin to intestinal epithelial cells in vitro protected against trypsin-mediated degradation of E-cadherin and TLR4 and reduced permeability of FITC-dextran across the monolayer. These results indicate that mucin plays an important role in the preservation of the mucosal barrier and that ischemia but not digestive enzymes disturbs mucin integrity, while digestive enzymes actively mediate epithelial cell disruption. Public Library of Science 2012-06-29 /pmc/articles/PMC3387149/ /pubmed/22768227 http://dx.doi.org/10.1371/journal.pone.0040087 Text en Chang et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Chang, Marisol Alsaigh, Tom Kistler, Erik B. Schmid-Schönbein, Geert W. Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine |
title | Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine |
title_full | Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine |
title_fullStr | Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine |
title_full_unstemmed | Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine |
title_short | Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine |
title_sort | breakdown of mucin as barrier to digestive enzymes in the ischemic rat small intestine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387149/ https://www.ncbi.nlm.nih.gov/pubmed/22768227 http://dx.doi.org/10.1371/journal.pone.0040087 |
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