Modulation of Systemic Metabolism by MMP‐2: From MMP‐2 Deficiency in Mice to MMP‐2 Deficiency in Patients
Bibliographic record
Abstract
ABSTRACT Matrix metalloproteinase‐2 (MMP‐2) is a 72‐kDa zinc‐ and calcium‐dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP‐2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP‐2 deficiency induces inflammation and deregulates metabolism. Humans and mice with a deficiency in MMP‐2 activity share a complex metabolic and inflammatory syndrome including cardiac dysfunction associated with congenital heart defects (in humans) and metabolic disorder (mice), arthritis, loss of bone mass, lipodystrophy, and delayed growth. The etiology of the inflammatory and metabolic syndrome in MMP‐2 deficiency is unknown and there is currently no cure for MMP‐2 deficiency in patients. Recent research suggests that the pathophysiology of MMP‐2 deficiency in mice and humans is influenced by a heart‐centric endocrine mechanism signaled by a cardiac‐specific secreted phospholipase A2 (cardiac sPLA2), which is released from cardiomyocytes in response to monocyte chemoattractant protein‐3, a proinflammatory cytokine normally cleaved and inactivated by MMP‐2. This review summarizes many important proteolytic functions of MMP‐2 and recapitulates recent reports linking the heart to systemic metabolic control through the MMP‐2/cardiac sPLA 2 axis. The authors suggest that MMP‐2 deficiency should, perhaps, be viewed and treated as an endocrine condition of excess sPLA2, a concept with particular importance for the therapeutic treatment of MMP‐2‐deficient patients. The possible existence of tissue‐specific MMP/cytokine/PLA 2 signaling systems is discussed. © 2016 American Physiological Society. Compr Physiol 6:1935‐1949, 2016.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".