Interaction of scleraxis and Smad‐dependent cardiac collagen expression
Bibliographic record
Abstract
Deposition of type I collagen is a hallmark of cardiac fibrosis. We have shown that the transcription factor scleraxis (Scx) is expressed in cardiac fibroblasts and is sufficient to regulate human collagen Iα2 (COLIα2) expression. Our objective was to study Scx interaction with the fibrotic Smad signalling pathway. We identified specific E box sites within the COLIα2 proximal promoter mediating transactivation by Scx. TGF-β1 augmented transactivation of the promoter by Scx, suggesting an additive effect of Scx with TGF-β1 signalling pathways. Inhibitory Smad7 partially blunted Scx-mediated COLIα2 promoter activation. Receptor Smad3 up-regulated whereas Smad7 down-regulated Scx expression in primary rat cardiac fibroblasts, suggesting cross-talk between Scx and Smad-mediated COLIα2 expression mechanisms. A dominant-negative Scx mutant abrogated COLIα2 promoter transactivation by TGF-β1, suggesting that interference with Scx function is sufficient to block pro-fibrotic signalling. We noted elevated Scx expression in the pressure-overloaded murine heart following thoracic aortic banding concomitant with increased type I collagen expression. These results support our hypothesis that Scx regulates collagen synthesis and hence may be an important novel target for developing anti-fibrotic therapies. Supported by Canadian Institutes of Health Research & St. Boniface Hospital Research Foundation.
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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".