Role of MMP‐2 activation in oncostatin‐M induced cardiomyocyte dedifferentiation
Bibliographic record
Abstract
Despite the dogma that adult mammalian cardiomyocyte is terminally differentiated, these cells have a discrete regenerative capacity in both acutely and chronically injured human hearts. Dedifferentiation of cardiomyocytes is an important source of cardiac progenitor cells facilitating cardiac repair. Oncostatin‐M (OSM) can induce cardiomyocyte dedifferentiation characterized by sarcomere degeneration. However, the detailed mechanism regarding the downstream execution of sarcomere degeneration remains unclear. Matrix metalloproteinase‐2 (MMP‐2) is an important intracellular protease known to cleave multiple sarcomeric proteins including α‐actinin, troponin‐I and titin. We studied the dynamics of sarcomere degeneration upon stimulation of neonatal rat ventricular cardomyocytes (NRVM) with OSM. As early as 48 hr after OSM (50ng/ml) treatment, changes in sarcomeric structure were observed. Z‐bands stained for α‐actinin were degenerated towards Z‐bodies and M lines stained for titin also showed a similar pattern. The beating rate of NRVM significantly decreased, consistent with the observed sarcomere degeneration. Western blots and gelatin zymography analysis show increased MMP‐2 activity and loss of α‐actinin and troponin I following OSM treatment. These results suggest the possible involvement of MMP‐2 in cardiomyocyte dedifferentiation stimulated by OSM. Funding: Canadian Institutes of Health Research
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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".