title: Jagged1/Notch3 Signaling Modulates Hemangioma-Derived Pericyte Proliferation and Maturation.
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.
authors.affiliation: Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ji
authors.forename: Siyuan
authors.initials: S
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D006391:Hemangioma / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D000072100:Jagged-1 Protein / Q000378:metabolism*; D008297:Male; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D000071656:Receptor, Notch3 / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1 / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000072100:Jagged-1 Protein; D000071656:Receptor, Notch3; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C497364:HEYL protein, human; C078493:HES1 protein, human