Hypertrophic Airway Smooth Muscle Mass Correlates with Increased Airway Responsiveness in a Murine Model of Asthma
Bibliographic record
Abstract
The increase of airway smooth muscle (ASM) mass in asthma results from hypertrophic and hyperplastic stimuli, and leads to an increase in cellular contractile proteins. However, little evidence correlates the relative contributions of hypertrophic and hyperplastic muscle with functional effects on airway resistance. We performed a ventilator-based assessment of respiratory mechanics and responsiveness to methacholine in a murine model of acute (3-week) ovalbumin (OVA)-induced airway inflammation, compared with a chronic (12-week) model. We correlated functional changes in airways Newtonian resistance (RN), peripheral tissue damping (G), and elastance (H) with the relative contributions of proliferation, hypertrophy, and apoptosis to increased ASM mass. Immunohistochemical analyses of treated (OVA-sensitized and OVA-challenged; OVA/OVA) and control (OVA-sensitized and saline-challenged; OVA/PBS) murine lungs showed an increase in ASM area in chronic, but not acute, OVA/OVA-treated mice that correlated positively with increased airway resistance to methacholine. Acute OVA/OVA-treated ASM exhibited an increase in proliferation with diminished apoptosis, which resolved in the chronic OVA/OVA model. Chronic OVA/OVA-treated ASM exhibited hypertrophy. Distinct temporal differences exist in the response of murine airways to antigenic challenge. We report that ASM proliferation and diminished apoptosis occur during the acute phase, followed by the development of smooth muscle hypertrophy and an increased muscle mass with chronic challenge, that correlate strongly with increased airway Newtonian resistance. The identification of a functionally relevant hypertrophic bronchial muscle mass highlights the possibility of regulating airway muscle hypertrophy as a novel therapeutic target in asthma.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".