Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD.
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 possi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5360340?pdf=render |
| _version_ | 1818361565374578688 |
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| author | Daniel Bergemalm Robert Kruse Maria Sapnara Jonas Halfvarson Elisabeth Hultgren Hörnquist |
| author_facet | Daniel Bergemalm Robert Kruse Maria Sapnara Jonas Halfvarson Elisabeth Hultgren Hörnquist |
| author_sort | Daniel Bergemalm |
| collection | DOAJ |
| description | 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 Galphai2-/- mouse feces relative to controls (fold change 27; p = 0.019). Other proteins found to be enriched in Gαi2-/- 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 Galphai2-/- 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. |
| first_indexed | 2024-12-13T21:18:42Z |
| format | Article |
| id | doaj.art-3f7c8e45b3a44e7a9e4a5aaffbb3b811 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:18:42Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3f7c8e45b3a44e7a9e4a5aaffbb3b8112022-12-21T23:31:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017427510.1371/journal.pone.0174275Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD.Daniel BergemalmRobert KruseMaria SapnaraJonas HalfvarsonElisabeth Hultgren HörnquistBACKGROUND: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 Galphai2-/- mouse feces relative to controls (fold change 27; p = 0.019). Other proteins found to be enriched in Gαi2-/- 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 Galphai2-/- 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.http://europepmc.org/articles/PMC5360340?pdf=render |
| spellingShingle | Daniel Bergemalm Robert Kruse Maria Sapnara Jonas Halfvarson Elisabeth Hultgren Hörnquist Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD. PLoS ONE |
| title | Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD. |
| title_full | Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD. |
| title_fullStr | Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD. |
| title_full_unstemmed | Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD. |
| title_short | Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD. |
| title_sort | elevated fecal peptidase d at onset of colitis in galphai2 mice a mouse model of ibd |
| url | http://europepmc.org/articles/PMC5360340?pdf=render |
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