FUNCTIONAL EXPRESSION OF THE EXTRACELLULAR CALCIUM‐SENSING RECEPTOR (CAR) ON AN ESOPHAGEAL EPITHELIAL CELL LINE (HET‐1A) AND IN HUMAN ESOPHAGUS
Bibliographic record
Abstract
Background: Human esophageal epithelial cells are regularly exposed to luminal contents and acid. The mechanisms that protect esophageal epithelium from this noxious environment are unknown. In other areas of the gastrointestinal tract CaR helps maintain epithelial homeostasis. The CaR is a G-protein coupled receptor that is activated by calcium and polyamines. This study was designed to determine the location and functional significance of CaR in the esophagus. Methods: CaR fluorescent immunostaining was performed on formalin fixed esophagus. Calcium and other CaR agonists were used to stimulate HET-1A cells, with IL-8 measured by ELISA. Calcium imaging was performed by loading HET-1A with Fluor 4 and measuring changes in fluorescence with CaR activation. Interfering RNA against the CaR was used to antagonize the effects of the CaR. Results: CaR immunoreactivity was robust in the esophageal basal layer and diminished in the non-replicating cells of the differentiated surface layer. CaR expression was confirmed in HET-1A cells by RT-PCR and immunocytochemistry. Extracellular Ca2+ stimulated secretion of the multifunctional cytokine IL-8 from HET-1A cells in a dose dependent manner (EC50~2.3 mM). Other CaR agonists including Mg2+ (20 mM), and spermine (1-10 mM) stimulated IL-8 secretion. Extracellular Ca2+ and spermine caused Ca2+ mobilization using Fluo-4 microspectroflurometry. HET-1A cells transiently transfected with siRNA directed against CaR did not exhibit Ca2+-stimulated increases in IL-8 secretion and intracellular Ca2+ release but demonstrated these responses when activated by acetylcholine (1 uM). Conclusion: The CaR is present on basal cells of the human esophagus and in HET-1A cells. Activation of the CaR on these cells mobilizes Ca2+ and leads to cytokine secretion. CaR is a new marker for basal esophageal cells and may play a protective role in esophageal homeostasis.
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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) | 0.003 | 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".