Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_A9B4457513BE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis.
Périodique
Inflammatory bowel diseases
Auteur(s)
Keppner A., Malsure S., Nobile A., Auberson M., Bonny O., Hummler E.
ISSN
1536-4844 (Electronic)
ISSN-L
1078-0998
Statut éditorial
Publié
Date de publication
12/2016
Peer-reviewed
Oui
Volume
22
Numéro
12
Pages
2824-2839
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)-induced colitis.
Wildtype, heterozygous (fr/+), and homozygous (fr/fr) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression.
In this study, a more detailed analysis on rat fr/fr colons revealed reduced numbers of crypt and goblet cells, and local angiodysplasia, as compared with heterozygous (fr/+) and wildtype littermates. Following 2% DSS treatment for 7 days followed by 7 days recovery, fr/fr animals lost body weight, and reached maximal diarrhea score and highest disease activity after only 3 days, and strongly increased cytokine levels. The histology score significantly increased in all groups, but fr/fr colons further displayed pronounced histological alterations with near absence of goblet cells, rearrangement of the lamina propria, and presence of neutrophils, eosinophils, and macrophages. Additionally, fr/fr colons showed ulcerations and edemas that were absent in fr/+ and wildtype littermates. Following recovery, fr/fr rats reached, although significantly delayed, near-normal diarrhea score and disease activity, but exhibited severe architectural remodeling, despite unchanged sodium transporter protein expression.
In summary, our results demonstrate a protective role of colonic prostasin expression against experimental colitis, and thus represent a susceptibility gene in the development of inflammatory bowel disease.

Mots-clé
Animals, Colitis/chemically induced, Colitis/genetics, Colon/metabolism, Cytoskeletal Proteins/metabolism, Dextran Sulfate, Disease Models, Animal, Genetic Predisposition to Disease, Inflammation/chemically induced, Inflammation/genetics, Intestinal Mucosa/metabolism, Rats, Serine Endopeptidases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2016 7:18
Dernière modification de la notice
20/08/2019 15:13
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