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| Status |
Public on Jul 17, 2009 |
| Title |
Dietary calcium inhibits colitis development in HLA-B27 transgenic rats |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Background and Aims: We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function is also relevant for inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental calcium on spontaneous colitis development in HLA-B27 transgenic rats, an experimental animal model of IBD.
Methods: HLA-B27 transgenic rats were fed a purified high-fat diet containing either a low or high calcium content (30 and 120 mmol CaHPO4/kg diet, respectively) for almost 7 weeks. Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability by measuring urinary CrEDTA excretion. Relative fecal dry-weight was determined to quantify diarrhea. Colonic inflammation was determined histologically, and by measuring mucosal interleukin-1β. In addition, colonic mucosal gene expression of individual rats was analyzed, using whole genome microarrays. Interesting results were verified by Q-PCR. Results: The high-calcium diet significantly prevented the increase in intestinal permeability and diarrhea with time in HLA-B27 rats developing colitis as compared to the low-calcium group. The histological colitis score and mucosal interleukin-1β levels were lower in high-calcium fed rats. Supplemental calcium prevented the colitis-induced increase in the expression of extracellular matrix remodeling genes (e.g. matrix metalloproteinases, procollagens and fibronectin), which was confirmed by Q-PCR.
Conclusions: Dietary calcium inhibits colitis development in HLA-B27 transgenic rats. Calcium prevents the colitis-related increase in intestinal permeability, diminishes diarrhea, and lowers the inflammatory response in the mucosa, resulting in less extracellular matrix breakdown.
Keywords: nutritional intervention
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| Overall design |
Female HLA-B27/β2-microglobulin transgenic rats on an inbred Fisher 344 background (n=8 in experimental group and n=9 in control group) (Taconic Farms, Inc, Germantown, NY), 8-10 weeks old and with a mean body weight of 128 g at the start of the experiment, were housed individually in metabolic cages. Animals were kept in a temperature- and humidity-controlled environment and in a 12-h light-dark cycle. Rats were fed a purified ‘humanized’ Western diet which contained in the control situation (per kg): 200 g acid casein, 326 g corn starch, 174 g glucose, 160 g palm oil, 40 g corn oil, 50 g cellulose and 5.16 g CaHPO4.2H2O (corresponding to 30 mmol calcium/kg diet; Sigma-Aldrich, St Louis, MO). Vitamins and minerals (other than calcium) were added to all diets according to the recommendations of the American Institute of Nutrition 1993.17 The experimental diet contained more calcium (120 mmol calcium/kg diet) at the expense of glucose.
All samples were individually labelled and hybridized (Cy5). Equal amounts of Cy3 cRNA of all animals were pooled to serve as standard reference pool.
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| Citation(s) |
19535420 |
| Submission date |
Apr 02, 2008 |
| Last update date |
Dec 21, 2016 |
| Contact name |
Marloes Schepens |
| Organization name |
NIZO food research
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| Street address |
P.O. Box 20
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| City |
Ede |
| ZIP/Postal code |
6710BA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL4135 |
Agilent-014879 Whole Rat Genome Microarray 4x44K G4131F (Feature Number version) |
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| Samples (17)
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| GSM278717 |
Low calcium, Colon mucosa, HLAB27, repl 1 |
| GSM278718 |
High calcium, Colon mucosa, HLAB27, repl 3 |
| GSM278719 |
Low calcium, Colon mucosa, HLAB27, repl 4 |
| GSM278720 |
Low calcium, Colon mucosa, HLAB27, repl 5 |
| GSM278721 |
Low calcium, Colon mucosa, HLAB27, repl 6 |
| GSM278722 |
Low calcium, Colon mucosa, HLAB27, repl 7 |
| GSM278723 |
Low calcium, Colon mucosa, HLAB27, repl 8 |
| GSM278724 |
High calcium, Colon mucosa, HLAB27, repl 9 |
| GSM278725 |
High calcium, Colon mucosa, HLAB27, repl 10 |
| GSM278726 |
Low calcium, Colon mucosa, HLAB27, repl 11 |
| GSM278727 |
High calcium, Colon mucosa, HLAB27, repl 13 |
| GSM278728 |
High calcium, Colon mucosa, HLAB27, repl 14 |
| GSM278729 |
Low calcium, Colon mucosa, HLAB27, repl 15 |
| GSM278730 |
Low calcium, Colon mucosa, HLAB27, repl 16 |
| GSM278731 |
High calcium, Colon mucosa, HLAB27, repl 17 |
| GSM278732 |
High calcium, Colon mucosa, HLAB27, repl 18 |
| GSM278856 |
High calcium, Colon mucosa, HLAB27, repl 2 |
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| Relations |
| BioProject |
PRJNA107117 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE11022_RAW.tar |
243.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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