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Elevated fecal peptidase D at onset of colitis in Galphai2(-/-) mice, a mouse model of IBD
Örebro University, School of Medical Sciences. Orebro University Hospital. Department of Gastroenterology.ORCID iD: 0000-0002-1906-0746
Örebro University, School of Medical Sciences. Orebro University Hospital.
Department of Microbiology and Immunology, University of Gothenburg, Institute of Biomedicine, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute of Medicine, Gothenburg, Sweden.
Örebro University, School of Medical Sciences. Orebro University Hospital. Department of Gastroenterology.ORCID iD: 0000-0003-0122-7234
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, e0174275Article in journal (Refereed) Published
Abstract [en]

Background: The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms.

Methods: Fecal samples were collected at onset of inflammation in Galphai2(-/-) mice, a well-described spontaneous model of chronic colitis, and from healthy littermates. The fecal proteome was analyzed by two-dimensional electrophoresis and quantitative mass spectrometry and results were then validated in a new cohort of mice.

Results: As a potential top marker of disease, peptidase D was found at a higher ratio in Galphai24mouse feces relative to controls (fold change 27; p = 0.019). Other proteins found to be enriched in Gai2(-/-) mice were mainly pancreatic proteases, and proteins from plasma and blood cells. A tendency of increased calprotectin, subunit S100-A8, was also observed (fold change 21; p = 0.058). Proteases are potential activators of inflammation in the gastrointestinal tract through their interaction with the proteinase-activated receptor 2 (PAR2). Accordingly, the level of PAR2 was found to be elevated in both the colon and the pancreas of Galphai24- mice at different stages of disease.

Conclusions: These findings identify peptidase D, an ubiquitously expressed intracellular peptidase, as a potential novel marker of colitis. The elevated levels of fecal proteases may be involved in the pathogenesis of colitis and contribute to the clinical phenotype, possibly by activation of intestinal PAR2.

Place, publisher, year, edition, pages
Public Library of Science , 2017. Vol. 12, no 3, e0174275
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-57622DOI: 10.1371/journal.pone.0174275ISI: 000399089000082PubMedID: 28323866Scopus ID: 2-s2.0-85016065409OAI: oai:DiVA.org:oru-57622DiVA: diva2:1094627
Note

Funding Agencies:

Bengt lhre research foundation  

Region Örebro county  OLL-526131 

Available from: 2017-05-10 Created: 2017-05-10 Last updated: 2017-05-10Bibliographically approved

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