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Mucosal healing progression after acute colitis in mice

BACKGROUND: Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are long...

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Autores principales: Vidal-Lletjós, Sandra, Andriamihaja, Mireille, Blais, Anne, Grauso, Marta, Lepage, Patricia, Davila, Anne-Marie, Gaudichon, Claire, Leclerc, Marion, Blachier, François, Lan, Annaïg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658396/
https://www.ncbi.nlm.nih.gov/pubmed/31367158
http://dx.doi.org/10.3748/wjg.v25.i27.3572
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author Vidal-Lletjós, Sandra
Andriamihaja, Mireille
Blais, Anne
Grauso, Marta
Lepage, Patricia
Davila, Anne-Marie
Gaudichon, Claire
Leclerc, Marion
Blachier, François
Lan, Annaïg
author_facet Vidal-Lletjós, Sandra
Andriamihaja, Mireille
Blais, Anne
Grauso, Marta
Lepage, Patricia
Davila, Anne-Marie
Gaudichon, Claire
Leclerc, Marion
Blachier, François
Lan, Annaïg
author_sort Vidal-Lletjós, Sandra
collection PubMed
description BACKGROUND: Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied. AIM: To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis. METHODS: C57BL/6 male mice were given 3.5% dextran sodium sulfate (DSS) in drinking water for 5 d. They were euthanized 2 (day 7), 5 (day 10), 8 (day 13), and 23 (day 28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16S rRNA sequencing. RESULTS: The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSS-treatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe (inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations (hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin (Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction. CONCLUSION: This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators.
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spelling pubmed-66583962019-07-31 Mucosal healing progression after acute colitis in mice Vidal-Lletjós, Sandra Andriamihaja, Mireille Blais, Anne Grauso, Marta Lepage, Patricia Davila, Anne-Marie Gaudichon, Claire Leclerc, Marion Blachier, François Lan, Annaïg World J Gastroenterol Basic Study BACKGROUND: Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied. AIM: To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis. METHODS: C57BL/6 male mice were given 3.5% dextran sodium sulfate (DSS) in drinking water for 5 d. They were euthanized 2 (day 7), 5 (day 10), 8 (day 13), and 23 (day 28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16S rRNA sequencing. RESULTS: The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSS-treatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe (inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations (hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin (Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction. CONCLUSION: This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators. Baishideng Publishing Group Inc 2019-07-21 2019-07-21 /pmc/articles/PMC6658396/ /pubmed/31367158 http://dx.doi.org/10.3748/wjg.v25.i27.3572 Text en ©The Author(s) 2019. 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 Basic Study
Vidal-Lletjós, Sandra
Andriamihaja, Mireille
Blais, Anne
Grauso, Marta
Lepage, Patricia
Davila, Anne-Marie
Gaudichon, Claire
Leclerc, Marion
Blachier, François
Lan, Annaïg
Mucosal healing progression after acute colitis in mice
title Mucosal healing progression after acute colitis in mice
title_full Mucosal healing progression after acute colitis in mice
title_fullStr Mucosal healing progression after acute colitis in mice
title_full_unstemmed Mucosal healing progression after acute colitis in mice
title_short Mucosal healing progression after acute colitis in mice
title_sort mucosal healing progression after acute colitis in mice
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658396/
https://www.ncbi.nlm.nih.gov/pubmed/31367158
http://dx.doi.org/10.3748/wjg.v25.i27.3572
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