Dysregulated actin cytoskeleton associated with barrier dysfunction in asthma
Bibliographic record
Abstract
Re‐establishment of a functional barrier following injury requires successful re‐differentiation of airway epithelial cells. A population of resident basal epithelial cells has been identified in human airways that express cytokeratin 5 (Krt5) and 14 (Krt14) and are capable of self‐renewal and generate differentiated epithelial cells during repair. Appropriately differentiated airway epithelium protects the lung parenchyma from inhaled particles/pathogens via luminal muco‐ciliary clearance and structural barrier conferred by tight junctions (TJ) which are regulated by a network of tissue‐specific inter‐ and intramembrane protein complexes linked to the underlying actin cytoskeleton. Contractility in actin filaments in turn drives junctional biogenesis that supports repair and return to steady state function. In patients with asthma, epithelial barrier is intrinsically compromised with loss of structural integrity perpetuated by a state of aberrant, non‐resolving repair. Therefore, understanding the expression and distribution of structural proteins that are required for junction formation will identify novel targets for pharmacological modulation to promote airway epithelial barrier repair in asthma. We have mapped temporal expression of TJ proteins during in vitro differentiation of bronchial epithelial cells from subjects with asthma and healthy donors. We identified disrupted localization of ZO‐1, claudin‐4 and ‐7 in early phases of differentiation in bronchial epithelial cells from asthmatic patients that coincided with persistent expression of Krt5 + and Krt14 + in resident Krt5 + basal cells, indicative of unresolved repair. This was associated with dysregulated arrangement in peri‐junctional actin cytoskeleton. In summary, we provide evidence that disrupted airway epithelial barrier in asthma is related to loss of F‐actin‐mediated localisation of TJ proteins and reduced transition of basal cells from a reparative phenotype to differentiated epithelial cells.
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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".