Jagged1/Notch3 Signaling Modulates Hemangioma-Derived Pericyte Proliferation and Maturation
Bibliographic record
Abstract
BACKGROUND: The Notch signaling pathway has been implicated in the pericyte phenotype, but its exact roles in hemangioma-derived pericytes (Hem-pericytes) remain ill defined. METHODS: Hem-pericytes were stimulated by immobilized recombinant Jagged1. The potential mechanisms of Notch-induced Hem-pericytes growth arrest were investigated by cell cycle assay, and the role of the Notch in promoting Hem-pericyte maturation was also analyzed by real-time PCR and western blot. RESULTS: Activation of Notch3 in Hem-pericytes significantly reduced cell proliferation and inhibited cell cycle transition. This event was associated with an increase in the levels of p21Cip1. Knockdown of p21Cip1 resulted in a significant rescue of Notch-induced cell growth arrest and an entry into the cell cycle. We showed that Jagged1 activation of Notch3 signaling upregulated the expression of the pericyte contractile markers smooth muscle myosin heavy chain (smMHC) and α-smooth muscle actin (αSMA), concomitant with an increase in the expression of myocardin in Hem-pericytes. We further revealed that the endothelial-derived Jagged1 modulated the Hem-pericyte phenotype via a contact-dependent mechanism. CONCLUSIONS: Our results demonstrated that Jagged1 activation of Notch3 resulted in a significant decrease in cell proliferation while concomitantly promoting Hem-pericyte maturation. These data provide initial evidence that Notch induces a quiescent phenotype in Hem-pericytes.
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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) | 0.001 | 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 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".