Pendrin Mediates Bicarbonate Secretion and Enhances CFTR Function in Airway Surface Epithelia
Bibliographic record
Abstract
Bicarbonate facilitates mucin unpacking and bacterial killing however its transport mechanisms in the airways are not well understood. cAMP stimulates anion efflux through the CFTR (ABCC7) anion channel and this is defective in CF. The anion exchanger pendrin (SLC26A4) also mediates HCO 3 − efflux and is upregulated by proinflammatory cytokines. Here we examined pendrin and CFTR expression and their contributions to HCO 3 − secretion by human nasal and bronchial epithelia. In native tissue, both proteins were most abundant at the apical pole of ciliated surface cells with little expression in submucosal glands. In well‐differentiated primary nasal and bronchial cell cultures, IL‐4 dramatically increased pendrin mRNA levels and apical immunostaining. Exposure to low‐Cl − apical solution caused intracellular alkalinization (ΔpH i ) that was enhanced 4‐fold by IL‐4 pretreatment. ΔpH i was unaffected by DIDS or CFTR inh ‐172 but was reduced by adenoviral shRNA targeting pendrin. Forskolin increased ΔpH i and this stimulation was prevented by CFTR inh ‐172 implicating CFTR, yet forskolin only increased ΔpH i after pendrin expression had been induced by IL‐4. The dependence of ΔpH i on pendrin suggests there is minimal electrical coupling between Cl − and HCO 3 − fluxes and that CFTR activation increases anion exchange‐mediated HCO 3 − influx. Conversely, inducing pendrin expression increased forskolin‐stimulated, CFTR inh ‐172‐sensitive current by ~2‐fold in epithelial and non‐epithelial cells. We conclude that pendrin mediates most HCO 3 − secretion across airway surface epithelium during inflammation and enhances electrogenic Cl − secretion via CFTR as described for other SLC26A transporters. Support or Funding Information Support: Cystic Fibrosis Canada, Canadian Institutes of Health Research, Canada Foundation for Innovation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 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".