A144 A NEW ROLE OF THE P2X7 RECEPTOR IN THE DEVELOPMENT OF THE INTESTINAL EPITHELIUM
Bibliographic record
Abstract
The P2X7 receptor (P2X7R) is an extracellular ATP-gated cation channel and its activation results in numerous downstream events including the release of inflammatory mediators and modulation of cell proliferation and death. P2X7R is expressed in intestinal epithelial cells (IEC), but its role is still poorly understood. We have shown that P2X7R was expressed in the top 2/3 of rat’s jejunum villi and that its activation decreased intestinal glucose absorption. At the transcriptional level, CCAAT/enhancer-binding protein β (C/EBPβ) drives P2RX7 gene expression in the small intestine. We observed that P2X7R expression coincides with CDX2 accumulation, an IEC transcription factor (TF) that regulates cell differentiation. CDX2 cooperates with several TFs such as GATA4. For this project, we hypothesized that P2X7R expression along the crypt-villus axis is differentially regulated, and that its expression is crucial for proper intestinal function. The project objectives were: 1) To elucidate P2X7R functional role in intestinal epithelium biology, and 2) To determine the nature of specific TFs involved in regulating P2RX7 promoter activity along the intestine crypt-villus axis. We took advantage of the Drosophila melanogaster model as it is devoid of P2X orthologs. The human P2RX7 (hP2RX7) was expressed specifically in the fly intestine and eyes and impacts on cell differentiation and tissue architecture characterized. Results were confirmed in wild type (P2rx7+/+) and knockout (P2rx7-/-) mice. Proliferation and migration was determined via BrdU incorporation. Impact on differentiation and polarization was characterized by measuring IEC specific markers expression, and cell junction integrity. Luciferase assays and Chromatin Immunoprecipitation (ChIP) were used to test for the capacity of the identified TF to activate and bind P2RX7 promoter region. Ectopic hP2RX7 expression in D. melanogaster eyes resulted in disorganization eye architecture, suggesting default in cell fate. In P2rx7-/- mouse jejunum, the absence of P2X7R expression was characterized by a decrease expression of sucrase-isomaltase, an enterocyte marker. These results suggest for a role of this receptor in the differentiation or polarization of epithelial cells. At the transcriptional level, luciferase assays have shown that GATA4 can activate hP2RX7 promoter. Beside our recent report on the role of P2X7R in IECs glucose absorption, the regulation of P2X7R expression and associated IEC functions are scarce but our results suggest a new role of P2X7R in IEC differentiation and identify the molecular events regulating its expression will lead to a better understanding of its function in IECs biology. NSERC
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".