P106 <break /> Role of Adenylate Cyclase Pathway in Prevention of Pulmonary Fibrosis
Bibliographic record
Abstract
Our previous studies have shown that blocking Ca2+-signaling reduces TGFβ-mediated extracellular matrix (ECM) deposition and progression of bleomycin-mediated fibrosis. As such, disruption of Ca2+-wave activity may prove useful in the treatment of pulmonary fibrosis. Prostaglandin E2 (PGE2) is known to exhibit certain anti-fibrotic effects. However, its effect on Ca2+-wave activity is unknown. In this study, we examined the role of PGE2 in regulating Ca2+ signaling in normal and diseased (IPF) fibroblasts. Human pulmonary fibroblasts (normal and IPF) were cultured and stimulated with either TGFβ or vehicle in the presence of various blockers. Ca2+ waves were monitored by confocal [Ca2+]i fluorimetry. RT-PCR and western blot were used to measure gene expression and different protein levels. We found that 500 nM PGE2 eliminated TGFβ-induced Ca2+ wave activity in normal fibroblasts and spontaneous Ca2+ wave activity in IPF fibroblasts. This inhibitory effect was mimicked by forskolin. We also found that PGE2 dramatically reduced the expression of ECM genes both in TGFβ-treated normal fibroblasts and in IPF fibroblasts. Immunofluorescence study showed that PGE2 inhibited the progression of fibroblast to myofibroblast transformation. We also examined the role of PGE2 in TGFβ-mediated other pathways.
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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 | 0.000 |
| 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) | 0.000 | 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".