Notch Signaling Regulates Platelet-Derived Growth Factor Receptor-β Expression in Vascular Smooth Muscle Cells

• DOI: 10.1161/circresaha.107.167965
• Publication Date: 2008-05-16T01:44:46Z
• Authors: Shaobo Jin; Emil M. Hansson; Saara Tikka; Fredrik Lanner; Cecilia Sahlgren; Filip Farnebo; Marc Baumann; Hannu Kalimo; Urban Lendahl
• Keywords: CADASIL; Notch proteins; Hes3 signaling axis

Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke dementia syndrome smooth muscle cell (VSMC) dysfunction. In this report, we link to platelet-derived growth factor (PDGF) signaling, key determinant VSMC biology, show that PDGF receptor ( PDGFR )-β novel immediate target gene. -β expression was upregulated by ligand induction or activated forms receptor. Moreover, upregulation response activation required signal integrator CSL. primary VSMCs, robustly leading an augmented intracellular stimulation. newborn Notch3 -deficient mice, PDGFR-β strongly reduced VSMCs later develop aberrant morphology. keeping this, also embryonic stem cells. Finally, from CADASIL patient carrying missense mutation, mRNA protein ligand-induced significantly reduced. sum, these data reveal hierarchy 2 systems, PDGF, vasculature provide insights into how dysregulated perturbs differentiation function.