RhoA-mediated signaling in Notch-induced senescence-like growth arrest and endothelial barrier dysfunction.

ABSTRACT:

Objective

Notch signaling has a critical role in vascular development and morphogenesis. Activation of Notch in endothelial cells led to a senescence-like phenotype with loss of barrier function. Our objective was to understand the molecular pathways mediating this phenotype.

Methods and results

Human primary endothelial cells increase expression of Notch receptors and ligands during propagation in vitro toward natural senescence. This senescence was induced at low passage with Notch activation. We characterized the pathways activated downstream of Notch signaling. Notch was activated by Delta-like 4 ligand or constitutively active Notch receptors and measured for cell proliferation, migration, and sprouting. Notch signaling triggered early senescence in low-passage cells, c

SUBMITTER: Venkatesh D 

PROVIDER: S-EPMC3252819 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature