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

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Version: Author's accepted manuscript
Serval ID
serval:BIB_A9B4457513BE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis.
Journal
Inflammatory bowel diseases
Author(s)
Keppner A., Malsure S., Nobile A., Auberson M., Bonny O., Hummler E.
ISSN
1536-4844 (Electronic)
ISSN-L
1078-0998
Publication state
Published
Issued date
12/2016
Peer-reviewed
Oui
Volume
22
Number
12
Pages
2824-2839
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.

Keywords
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
Yes
Create date
25/10/2016 7:18
Last modification date
17/09/2020 8:18
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