Stretch-induced Activation of Transforming Growth Factor-β1 in Pulmonary Fibrosis
Bibliographic record
Abstract
RATIONALE: Recent findings suggesting transforming growth factor (TGF)-β1 activation by mechanical stimuli in vitro raised the question of whether this phenomenon was relevant in vivo in the context of pulmonary fibrosis. OBJECTIVES: To explore the effect of mechanical stress on TGF-β1 activation and its signaling pathway in rat and human fibrotic lung tissue using a novel ex vivo model. METHODS: Rat lung fibrosis was induced using transient gene expression of active TGF-β1. Lungs were harvested at Day 14 or 21 and submitted to various stimuli in a tissue bath equipped with a force transducer and servo-controlled arm. MEASUREMENTS AND MAIN RESULTS: Fibrotic lung strips responded to tensile force by releasing active TGF-β1 from latent stores with subsequent increase in tissue phospho-Smad2/3. In contrast, measurable active TGF-β1 and phospho-Smad2/3 were not induced by mechanical stress in nonfibrotic lungs. Protease inhibition did not affect the release of active TGF-β1. A TGF-β1 receptor inhibitor, Rho-associated protein kinase inhibitor, and αv integrin inhibitor all attenuated mechanical stretch-induced phospho-Smad2/3 in fibrotic lung strips. Furthermore, the induction of phospho-Smad2/3 was enhanced in whole fibrotic rat lungs undergoing ventilation pressure challenge compared with control lungs. Last, tissue slices from human lung with usual interstitial pneumonia submitted to mechanical force showed an increase in TGF-β1 activation and induction of phospho-Smad2/3 in contrast with human nonfibrotic lungs. CONCLUSIONS: Mechanical tissue stretch contributes to the development of pulmonary fibrosis via mechanotransduced activation of TGF-β1 in rodent and human pulmonary fibrosis.
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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 | 0.001 |
| 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 | 0.001 |
| 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".