Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis. Issue 12 (December 2016)

• Record Type: Journal Article
• Authors: Keppner, Anna; Malsure, Sumedha; Nobile, Antoine; Auberson, Muriel; Bonny, Olivier; Hummler, Edith
• Is Part Of: Inflammatory bowel diseases. Volume 22:Issue 12(2016:Dec.)
• Publication Date: 2016-12
• Subjects: prostasin -- dextran sodium sulfate -- inflammatory bowel disease; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000940
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: 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. Methods: Wildtype, heterozygous ( fr CR /+ ), and homozygous ( fr CR /fr CR ) 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. Results: In this study, a more detailed analysis on rat fr CR /fr CR colons revealed reduced numbers of crypt and goblet cells, and local angiodysplasia, as compared with heterozygous ( fr CR /+ ) and wildtype littermates. Following 2% DSS treatment for 7 days followed by 7 days recovery, fr CR /fr CR 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 CR /fr CR 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 CR /fr CR colons showed ulcerations and edemas that were absent in fr CR /+ and wildtype littermates. Following recovery, fr CR /fr CR rats reached, although significantly delayed, near-normal diarrhea score and disease activity, but exhibited severe architectural remodeling, despite unchanged sodium transporter protein expression. Conclusions: 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. Abstract : Article first published online 12 October 2016.