Homotypic and Endothelial Cell Adhesions via N-Cadherin Determine Polarity and Regulate Migration of Vascular Smooth Muscle Cells
Bibliographic record
Abstract
Migration of smooth muscle cells from the arterial media to the intima is central to several vascular pathologies including restenosis. This study demonstrates that, like directional migration of other cells, smooth muscle migration is accompanied by a dramatic, polarized reorganization of the cell cytoskeleton that is accompanied by activation of the Rho GTPase Cdc42 and inactivation of glycogen synthase kinase-3beta. We also show, for the first time, that signals generated at the posterior-lateral aspects of wound edge cells by the cell-cell adhesion molecule N-cadherin are required for polarization and rapid migration of vascular smooth muscle. Importantly, when a cohort of migrating smooth muscle cells encounter CHO cells or the A10 smooth muscle cell line, neither of which expresses N-cadherin, polarity is only slightly suppressed. However, when smooth muscle cells encounter stably transfected, N-cadherin-expressing A10 cells or (N-cadherin-expressing) vascular endothelium, they rapidly lose their polarized phenotype. The latter finding indicates that endothelial signaling to innermost smooth muscle cells via N-cadherin may be critical to normal vessel wall stability. We infer that asymmetrical distribution of N-cadherin is necessary for the establishment of cell polarity during migration and that N-cadherin ligation is highly effective in abrogating polarized migration. Finally, we showed that endothelial cell polarity does not depend on N-cadherin; therefore, this molecule may be an attractive target for therapies to prevent restenosis without suppressing endothelial repair and risking late thrombosis.
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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".