MAPK signaling regulates endothelial cell assembly into networks and expression of MT1-MMP and MMP-2
Bibliographic record
Abstract
Microvascular endothelial cells embedded within three-dimensional (3D) type I collagen matrixes assemble into cellular networks, a process that requires the upregulation of membrane type 1 (MT1) matrix metalloproteinase (MMP) and MMP-2. The purpose of this study was to identify the signaling pathways responsible for the transcriptional activation of MT1-MMP and MMP-2 in endothelial cells in 3D collagen lattices. We hypothesized that the 3D type I collagen induction of MT1-MMP and MMP-2 is mediated by the mitogen-activated protein kinase family of enzymes. Here, we show that 3D type I collagen elicits a persistent increase in ERK1/2 and JNK activation and a decrease in p38 activation. Inhibition of ERK1/2 or JNK disrupted endothelial network formation in 3D type I collagen lattices, whereas inhibition of p38 promoted network formation. mRNA levels of both MT1-MMP and MMP-2 were attenuated by ERK1/2 inhibition but unaffected by either JNK or p38 inhibition. By contrast, expression of constitutively active MEK was sufficient to stimulate MMP-2 production in a monolayer of endothelial cells cultured on type I collagen. These results provide evidence that signaling through both ERK1/2 and JNK regulates endothelial assembly into cellular networks but that the ERK1/2 signaling cascade specifically regulates network formation and the production of both MT1-MMP and MMP-2 genes in response to 3D type I collagen.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".