Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia
Bibliographic record
Abstract
Chronic inflammatory bowel diseases (IBD) are associated with an abnormal immune response to intestinal bacteria. Although the pro-inflammatory mediator osteopontin (OPN) is upregulated in IBD, its role in disease pathogenesis remains unclear. The aim of this study, therefore, was to determine the role of OPN in mediating host responses to a non-invasive intestinal bacterial pathogen, using Citrobacter rodentium infection of mice as a murine model of IBD, as well as infecting mouse-derived OPN+/+ and OPN-/- fibroblasts. OPN-/-” and wild-type (WT) mice were inoculated with either C. rodentium or LB broth (as sham control). Colonic epithelial cell hyperplasia, which is the hallmark of C. rodentium infection, was reduced in infected OPN-/- mice (218±13μm, N = 15) relative to infected WT mice (295±15μm; N=8; p=0.01), and daily rectal administration of OPN to OPN-/-” mice partially restored the WT phenotype (239±21μm; N = 6; p<0.05). Colonization of mice with C. rodentium was also reduced in OPN-/- mice (3.9×104±3.2×103 vs 2.8×105±8×104; p<0.005). An increase in spleen weight and in the number of splenocytes observed in infected WT mice was absent in null mice. By contrast, there was no difference in body weight, disease activity, bacterial translocation, and overall histology score between infected WT and infected OPN-/- mice. While lack of OPN did not decrease bacterial adhesion to mouse fibroblasts (54±21 vs. 44±15 bacteria/cell; N = 3; p>0.05), rearrangements of the cytoskeleton, demonstrated by attaching and effacing lesions, were reduced in cells derived from OPN-/- mice and restored in OPN-/- cell rescued with human OPN by stable transfection and with exogenous application of OPN. Lack of OPN results in decreased pedestal formation and colonic epithelial cell hyperplasia in response to C. rodentium infection, indicating that OPN mediates signaling events that impact on the pathogenesis of disease through rearrangements of the host cell cytoskeleton. These findings demonstrate a role for OPN in mediating host responses to injury and inflammation caused by a microbial pathogen, and could thereby explain its role in the pathogenesis of IBD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".