A209 EVALUATION OF THE ROLE OF DUSP1 AND DUSP16 GENES IN THE REGULATION OF INTESTINAL EPITHELIAL FONCTIONS
Bibliographic record
Abstract
Abstract Background Inflammatory bowel disease (IBD) is associated with inflammation of the gastrointestinal tract, resulting from a dysregulation of the immune response to microbes in the intestinal lumen. Dr. Rioux’s laboratory has identified over 200 genomic regions associated with IBD. However, the challenge lies in identifying the causal gene in many of these. To address this problem, our laboratory completed a transcriptomic screen following overexpression of IBD-associated genes in intestinal epithelial cells. This study demonstrates that DUSP1 and DUSP16, two phosphatases targeting MAP Kinases (MAPKs), regulate the expression of several shared genes involved in intestinal differentiation and homeostasis. Aims Our research hypothesis is that the DUSP1 and DUSP16 genes participate in the regulation of biological processes involved in IBD and critical for the integrity of the intestinal barrier. More specifically, we want to determine how a reduction in DUSP1 and DUSP16 affects the biological pathways leading to the regulation of epithelial junction integrity, as well as inflammasome activation and IL-18 secretion. Methods In this project, we studied Caco-2 cells expressing DUSP1 or DUSP16 knockdown and their effect on intestinal epithelial cell functions. Among other things, we observed the cells’ ability to form a tight monolayer in 2D and spheroids in 3D. We also analyzed by Western blotting the impact of knockdowns on inflammasome formation and normal activity. Results Our results show that Dusp1 and DUSP16 knockdowns disrupt the ability of Caco-2 cells to form a tight monolayer and to form spheroids. In addition, our inflammasome analysis shows that KDs deregulate inflammasome activity. Conclusions These results demonstrate that decreased expression of the DUSP1 and DUSP16 genes impacts several functions essential to the maintenance of intestinal epithelial cell homeostasis, such as intestinal barrier integrity and inflammasome activation. Funding Agencies CIHRNIH
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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) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".