Mucosal healing progression after acute colitis in mice.
Animals
Cell Movement
Cell Proliferation
Colitis, Ulcerative
/ chemically induced
Colon
/ cytology
Dextran Sulfate
/ toxicity
Disease Models, Animal
Gastrointestinal Microbiome
/ immunology
Humans
Inflammation Mediators
/ immunology
Intestinal Mucosa
/ cytology
Male
Mice
Mice, Inbred C57BL
Permeability
RNA, Ribosomal, 16S
Regeneration
/ immunology
Acute colitis
Colon luminal environment
Dextran sodium sulfate-induced colitis
Dysbiosis
Epithelial repair
Journal
World journal of gastroenterology
ISSN: 2219-2840
Titre abrégé: World J Gastroenterol
Pays: United States
ID NLM: 100883448
Informations de publication
Date de publication:
21 Jul 2019
21 Jul 2019
Historique:
received:
09
04
2019
revised:
27
05
2019
accepted:
08
06
2019
entrez:
2
8
2019
pubmed:
2
8
2019
medline:
21
1
2020
Statut:
ppublish
Résumé
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. To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31367158
doi: 10.3748/wjg.v25.i27.3572
pmc: PMC6658396
doi:
Substances chimiques
Inflammation Mediators
0
RNA, Ribosomal, 16S
0
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3572-3589Déclaration de conflit d'intérêts
Conflict-of-interest statement: The authors have nothing to disclose.
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