Cdc42 increases activation of MMP‐2 in endothelial cells
Bibliographic record
Abstract
Angiogenesis is stimulated by VEGF and requires basement membrane degradation by the matrix metalloproteinases (MMPs). VEGF induces increased membrane type 1‐MMP on the cell surface (required for MMP‐2 activation) and signals through the RhoGTPase family members. The RhoGTPases and the MAPK p38 are known for their roles upstream of actin cytoskeleton reorganization and are purported to regulate angiogenesis. We hypothesize that Cdc42 mediates the effects of VEGF on activation of MMP‐2 via p38 and actin cytoskeleton reorganization. To investigate this we manipulated Cdc42 signaling with a constitutively active Cdc42 (CA‐Cdc42) TAT‐fusion protein and observed the effects in rat skeletal muscle endothelial cells. Confocal microscopy demonstrated that CA‐Cdc42 increased cortical actin and the proportion of retracted or protruded cells similar to VEGF‐induced actin stress fibre depolymerization. CA‐Cdc42 treatments resulted in increased phospho‐p38 levels as seen with VEGF via western blotting. Furthermore, MMP‐2 activation increased in cells treated with CA‐Cdc42 or VEGF independent of new protein synthesis, as tested by gelatin zymography. This evidence suggests that Cdc42 may mediate the effects of VEGF on actin cytoskeleton reorganization, p38 phosphorylation and the levels of active MMP‐2. Funded by NSERC.
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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) | 0.000 | 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) | 0.003 | 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".