Abstract 12470: miR-187 Mimic Targets Pro-Inflammatory Cytokynes in Cardiomyocytes Treated With Bacterial Endotoxin
Bibliographic record
Abstract
Introduction: 1 in 18 Canadians dies from sepsis, a life-threatening dysfunction caused by a dysregulated host response to infection which can lead to sepsis-induced Cardiac dysfunction. In the past, we have shown that administration of mesenchymal stem cells (MSCs) in the cecal ligation and puncture (CLP) model of polybacterial sepsis leads to the mitigation of sepsis-induced cardiac dysfunction by modulating microRNAs in the septic heart. Differential expression of miRNAs alters mRNA expression profile leading to a change in cellular response. In our CLP model, we identified miR-187 as a host-derived MSC-regulated miRNA. Hypothesis: Here we investigate the broader immunoregulatory of miR-187. Therefore, we tested the hypothesis that miRNA-187 inversely regulates sepsis-induced cardiac dysfunction by attenuating pro-inflammatory gene expression. Methods: Primary cardiomyocytes were isolated from 1-2 days old CD1 neonates. Cultured cells were transfected with miR-187 mimic (25 nM/mL) for 24 hours. Transfected cells were then subsequentially exposed to lipopolysaccharide (LPS, 1 μg/mL) for an additional 24 hours post-transfection. We chose to measure the expression of pro and anti-inflammatory cytokines and some cardiac injury markers via Real-Time Polymerase Chain Reaction (RT-qPCR). Results: Cardiomyocytes treated with bacterial LPS showed a significant decline in expression of miR-187 (n=4, p<0.05) and a significant surge (n=4, p<0.05) in the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNFα and IL-12 in comparison to untreated cells. Conversely, LPS-stimulated cardiomyocytes transfected with exogenous miR-187 mimic versus non-transfected LPS-stimulated cardiomyocytes demonstrated reduced expression of IL-1β, IL-6, and IL-12 (n=3, p<0.05) and Fasl, S100A4 and S100A9 (n=3, p<0.05). Conclusions: Transfecting neonatal cardiomyocytes with mimic miR-187 in the presence of LPS decreases the production of key inflammatory genes involved in sepsis-induced cardiac dysfunction. Our findings show miR-187 to be a potential therapeutic target to improve cardiac function in a pre-clinical model of sepsis by reducing pro-inflammatory cytokine expression.
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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) | 0.001 | 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".