Abstract 507: Homotypic Interactions and Networking Among Vascular Smooth Muscle Cells Are Mediated by a Transforming Growth Factor-ß-Cadherin-11 Axis
Bibliographic record
Abstract
Formation and stabilization of arteries requires that smooth muscle cells (SMCs) coalesce into sheets and layers of co-aligned cells. However, the molecular basis by which SMCs form a stable collective is largely unknown. To elucidate key steps in forming an ordered SMC collective, we tracked differentiation-competent human SMCs as they were induced to shift from individual behavior to collective patterning. Transmission electron microscopy identified the acquisition of well-developed adherens junctions during this transition. As well, immunofluorescence microscopy revealed both cadherin-2 and -11-containing intercellular junctions, the latter not previously identified in vascular SMCs. Furthermore, these junctions underwent striking elongation during collectivization (3-fold elongation, p<0.001), effectively strapping cells to each other. Adherens junction maturation was associated with down-regulation of phosphorylated SMAD2 and could be reversed by addition of transforming growth factor-beta (TGFß)1 (p<0.001). Time-lapse video microscopy revealed that collectivization of SMCs was partially inhibited by a blocking antibody to cadherin-2 (p=0.021) and strikingly inhibited by a cadherin-11 blocking antibody (p<0.001). Imaging of Fura2-loaded SMCs revealed coordinated calcium transients among stably contacting SMCs (p<0.001), but these were inhibited when cadherin-11 was blocked (p<0.001). Immunostaining of small and medium sized arteries in the mouse hindlimb identified OB-cadherin in both endothelial and SMC layers. Conclusions: Cadherin-11 is present in the artery wall and mediates the acquisition of stable and functional homotypic interactions among contacting SMCs. This TGFß-regulatable phenomenon of collectivization could be critical to vascular development, repair, and regeneration.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".