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Regulation of intestinal permeability: The role of proteases

The gastrointestinal barrier is - with approximately 400 m(2) - the human body’s largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host cont...

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Autores principales: Van Spaendonk, Hanne, Ceuleers, Hannah, Witters, Leonie, Patteet, Eveline, Joossens, Jurgen, Augustyns, Koen, Lambeir, Anne-Marie, De Meester, Ingrid, De Man, Joris G, De Winter, Benedicte Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374123/
https://www.ncbi.nlm.nih.gov/pubmed/28405139
http://dx.doi.org/10.3748/wjg.v23.i12.2106
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author Van Spaendonk, Hanne
Ceuleers, Hannah
Witters, Leonie
Patteet, Eveline
Joossens, Jurgen
Augustyns, Koen
Lambeir, Anne-Marie
De Meester, Ingrid
De Man, Joris G
De Winter, Benedicte Y
author_facet Van Spaendonk, Hanne
Ceuleers, Hannah
Witters, Leonie
Patteet, Eveline
Joossens, Jurgen
Augustyns, Koen
Lambeir, Anne-Marie
De Meester, Ingrid
De Man, Joris G
De Winter, Benedicte Y
author_sort Van Spaendonk, Hanne
collection PubMed
description The gastrointestinal barrier is - with approximately 400 m(2) - the human body’s largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extra-intestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.
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spelling pubmed-53741232017-04-12 Regulation of intestinal permeability: The role of proteases Van Spaendonk, Hanne Ceuleers, Hannah Witters, Leonie Patteet, Eveline Joossens, Jurgen Augustyns, Koen Lambeir, Anne-Marie De Meester, Ingrid De Man, Joris G De Winter, Benedicte Y World J Gastroenterol Review The gastrointestinal barrier is - with approximately 400 m(2) - the human body’s largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extra-intestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases. Baishideng Publishing Group Inc 2017-03-28 2017-03-28 /pmc/articles/PMC5374123/ /pubmed/28405139 http://dx.doi.org/10.3748/wjg.v23.i12.2106 Text en ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Review
Van Spaendonk, Hanne
Ceuleers, Hannah
Witters, Leonie
Patteet, Eveline
Joossens, Jurgen
Augustyns, Koen
Lambeir, Anne-Marie
De Meester, Ingrid
De Man, Joris G
De Winter, Benedicte Y
Regulation of intestinal permeability: The role of proteases
title Regulation of intestinal permeability: The role of proteases
title_full Regulation of intestinal permeability: The role of proteases
title_fullStr Regulation of intestinal permeability: The role of proteases
title_full_unstemmed Regulation of intestinal permeability: The role of proteases
title_short Regulation of intestinal permeability: The role of proteases
title_sort regulation of intestinal permeability: the role of proteases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374123/
https://www.ncbi.nlm.nih.gov/pubmed/28405139
http://dx.doi.org/10.3748/wjg.v23.i12.2106
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