Matrix metalloproteinase‐2 mediate oncostatin‐M induced cardiomyocyte dedifferentiation (1151.2)
Bibliographic record
Abstract
Dedifferentiated cardiomyocytes are an important source of cardiac progenitor cells facilitating cardiac repair. Cardiomyocyte dedifferentiation induced by oncostatin‐M (OSM) is characterized by progressive sarcomere degeneration. However, the mechanism regarding the execution of sarcomere degeneration remains unclear. Matrix metalloproteinase‐2 (MMP‐2) is a key intracellular protease abundantly expressed in cardiomyocytes. We hypothesized that MMP‐2 may be involved in cardiomyocyte dedifferentiation. We performed confocal immunofluorescence and biochemical studies to explore the role of MMP‐2 in OSM‐induced dedifferentiation of neonatal rat ventricular myocytes (NRVM). Cells treated with OSM (10‐200 ng/ml for 1‐5 days) showed a dose and time‐dependent loss of sarcomeric α‐actinin and troponin‐I. The mature sarcomere transformed to a pattern resembling a less developed sarcomere (Z‐disks transformed into Z‐bodies usually found in immature myofibrils). Western blots and gelatin zymography showed that OSM treatment dose‐dependently increased MMP‐2 activity. Both selective MMP‐2 inhibitor (ARP100, 100 µM) and pan‐MMP inhibitors (GM6001, 5 µM) rescued OSM‐induced sarcomere degeneration. These results suggest that intracellular MMP‐2 mediates sarcomere degeneration in OSM‐induced cardiomyocyte dedifferentiation and potentially contributes to cardiomyocyte regeneration. Grant Funding Source : The Canadian Institutes of Health Research (CIHR)
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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 | 0.001 | 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 | 0.001 |
| 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".