Mechanical Wound and Loss of Cell Polarity decrease ENaC Expression in Alveolar Epithelial Cells
Bibliographic record
Abstract
The epithelial Na channel (ENaC) activity and expression is an essential component for resorption of lung edema during acute respiratory distress syndrome (ARDS). We reported previously that PAMP or pro-inflammatory cytokines present in ARDS downregulate ENaC expression and activity in alveolar epithelial cells, suggesting that pro-inflammatory environment is detrimental for ENaC function. During ARDS lung injury, there is an extensive alveolar epithelial dysfunction leading to cell mortality. Using alveolar epithelial cells in primary culture, we tested how disruption of barrier integrity could modulate ENaC expression in a model of mechanical wounding (MW). We found that α,β,γENaC mRNA expression are downregulated by ~50% at 6h and 24h following wounding. Chelation of intracellular Ca++ with BAPTA-AM, inhibition of purinergic signaling with suramin or PKC with Gö6976 cannot inhibit this process. Disruption of cell junctions with a 5min EDTA treatment or actin disruption with cytochalasin D has the same effect on ENaC expression. In addition to ENaC, MW and EDTA upregulate junction components expression such as Cldn3, Cldn4 , Cldn7, Cdh1 and Itgb3 at 6h while their respective level is back to control after 24h. Altogether, these results suggest that mechanical wounding and loss of cell polarity trigger a complex gene expression program in alveolar epithelial cells that could promote cell repair of the wounded epithelium. These results show that during lung injury, the loss of integrity of the alveolar epithelium is also a factor that downregulates per se ENaC expression. In addition to its functional role, ENaC downregulation seems a very sensitive marker of alveolar epithelial injury.
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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 | 0.000 | 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) | 0.000 | 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".