Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking
Bibliographic record
Abstract
Abstract The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus ( BO ) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium ( HET ‐1A) and BO ( QH ) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α 3 , α 4, α 5 , α 6 and α ν ). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease ( GORD ) and in patient tissue microarrays. The bile acid deoxycholic acid ( DCA ) specifically reduced adhesion of HET ‐1A cells to vitronectin and reduced cell‐surface expression of integrin‐α ν via effects on endocytic recycling processes. Increased expression of integrin‐α v was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin‐α ν was observed in QH BO cells compared to HET ‐1A cells. QH cells were resistant to DCA ‐mediated loss of adhesion and reduction in cell‐surface expression of integrin‐α ν . We demonstrated that a specific component of the gastric refluxate, DCA , affects the epithelial barrier through modulation of integrin α ν expression, providing a novel mechanism for bile acid‐mediated erosion of oesophageal squamous epithelium and promotion of BO . Strategies aimed at preventing bile acid‐mediated erosion should be considered in the clinical management of patients with GORD .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 teacher head, 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".