Bibliographic record
Abstract
Objective: Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium.One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumulation in the extracellular matrix.Continuous FGF-2 release would require a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity in cardiomyocytes as a potential target for optimizing cardioprotection.Methods and results: To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM), were transfected with f 1 or 0.1 kb of rat FGF-2 promoter sequences linked to luciferase, À1058FGF -2p.luc and À110FGF -2p.luc, and treated with or without FGF-2.FGF-2 promoter activity was significantly increased f 2.5-fold with both genes.The proximal promoter region of rat FGF-2 contains putative binding sites for the early growth response-1 (Egr-1) and stimulating protein 1 (Sp1) transcription factors.Overexpression of Egr-1 and Sp1 increased À1058FGF -2p.luc expression by 4.4-and 8.7-fold, respectively.Mutation of Egr-1 and overlapping Sp1 sites did not blunt the response of À110FGF -2p.luc to FGF-2 treatment but did significantly reduce basal promoter activity.Transgenic mice expressing À1058FGF -2p.luc were treated with isoproterenol (IsP) to increase heart rate and endogenous FGF-2 release.FGF-2 promoter activity was stimulated significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels were also detected.In contrast, no effect of IsP was seen on À1058FGF -2p.luc or À110FGF -2p.luc in transfected NRCMs.Conclusions: FGF-2 released from cardiomyocytes may act to regulate its own synthesis at the transcriptional level.The mechanism does not appear to require an intact Egr-1 site in the proximal promoter region.This may, however, reflect redundancy in the control of FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| 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".