Notch 1 and 3 receptors modulate vascular smooth muscle cell growth, apoptosis and migration via a CBF‐1/RBP‐Jk dependent pathway

Abstract
SPECIFIC AIMSVascular smooth muscle cell (SMC) fate decisions (cell growth, migration, and apoptosis) are fundamental features in the pathogenesis of vascular disease. The aim of the study was to examine the role of activated Notch 1 and Notch 3 receptors (Notch IC, the cleaved intracellular domains) in controlling SMC fate in vitro. Using adult rat SMC in culture, we examined the role of CBF-1/RBP-Jk-dependent gene expression in mediating the effects of Notch 1 and 3 IC signaling on SMC growth, apoptosis, and migration.PRINCIPAL FINDINGS1. Notch 1 and 3 IC receptors activate notch target genes in a CBF-1-dependent manner in SMCAssessment of Notch signaling in rat SMC in vitro using Western blot analysis, luciferase reporter assays, and real-time PCR revealed that Hairy Enhancer of Split (hes-1 and -5) and related hrt’s (hrt-1, -2, and -3) are direct downstream target genes of Notch 1 and 3 IC in SMC and identified an essential role for the nuclear protein CBF-1/RBP-Jk in their regulation. Overexpression ...
Funding Information
  • Higher Education Authority
  • National Institutes of Health (HL59696, AA‐12610)