Notch2 suppression mimicking changes in human pulmonary hypertension modulates Notch1 and promotes endothelial cell proliferation
Sanghamitra Sahoo, Yao Li, Daniel Simões de Jesus, John Sembrat, Mauricio Rojas, Elena A. Goncharova, Eugenia Cifuentes-Pagano, Adam C. Straub, Patrick J. Pagano
Abstract
This study demonstrates a previously unidentified role for Notch2 in the maintenance of lung vascular endothelial cell quiescence and pulmonary artery hypertension (PAH). A key novel finding is that Notch2 suppression activates Notch1 via Rb-E2F1-mediated signaling and induces proliferation and apoptosis resistance in human pulmonary artery endothelial cells. Notably, PAH patients show reduced levels of endothelial Notch2 in their pulmonary arteries, supporting Notch2 as a fundamental driver of PAH pathogenesis.
Topics & Concepts
HES1Notch signaling pathwayCancer researchBiologyDownregulation and upregulationGene knockdownCell growthCell biologyEndothelial stem cellApoptosisContext (archaeology)EndocrinologyInternal medicineSignal transductionMedicineGeneIn vitroBiochemistryGeneticsPaleontologyPulmonary Hypertension Research and TreatmentsPI3K/AKT/mTOR signaling in cancerVascular Anomalies and Treatments