In vivo effects of TGF-β1 in lung surfactant regulation, lung meachanics amd structure
Bibliographic record
Abstract
Transforming growth factor beta 1 (TGF-β1) is a signalling protein with a wide range of biological activities. TGF-β1 is thought to have a pivotal role in fibrogenesis, where TGF-β1 induces myofibroblast migration and increases extracellular matrix synthesis, including collagen. Moreover, it has been described that TGF-β1 is a negative modulator of the regulation of surfactant associated proteins A (SP-A), B (SP-B) and C (SP-C) in vitro. Pulmonary surfactant is a lipid-protein complex that lowers surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to collapse alveoli. SP-B and SP-C deficiency has been found in patients suffering from lung diseases and related to potential mechanical stress of the lung epithelium. We have characterized lung surfactant protein composition 1 and 2 weeks after adenoviral mediated gene transfer of active TGF-β1 into lungs. Gene expression of surfactant proteins is down-regulated pointing at deficient transcriptional regulation that might include a deficient activity of TTF-1, during TGF-β1 overexpression. Deficiency on SP-B and SP-C at early stages correlates with high surface tension under dynamic cycling of isolated surfactant in Captive Bubble Surfactometry (CBS). In addition, high surface tension correlates with decreased quasistatic lung compliance and increased collapsibility of distal airspaces. Stereological data demonstrate a correlation between septal wall thickness and quasistatic compliance 2 weeks after gen-transfer. At the ultrastructural level thickening of septal walls, could be attributed to an increase in interstitial cells, formation of dense alveolar oedema and increase in profiles of epithelial type II (AEII) cells. The latter could be also attributed to Epithelial to Mesenchymal Transition (EMT), indicated by down-regulation of epithelial markers associated to up-regulation of mesenchymal molecular markers. We can conclude that in vivo TGF-β1 is a strong negative regulator of surfactant metabolism, originating a mechanical stress that may contribute to EMT at following stages.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.003 |
| 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 | 0.001 |
| 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".