ZFIN ID: ZDB-PUB-071125-2
Neuropilin-1 Modulates p53/Caspases Axis to Promote Endothelial Cell Survival
Wang, L., Dutta, S.K., Kojima, T., Xu, X., Khosravi-Far, R., Ekker, S.C., and Mukhopadhyay, D.
Date: 2007
Source: PLoS One   2(11): e1161 (Journal)
Registered Authors: Ekker, Stephen C., Xu, Xiaolei
Keywords: Apoptosis, VEGF signaling, Embryos, Zebrafish, Fluorescence imaging, Morpholino, Apoptotic signaling cascade, Forkhead box
MeSH Terms:
  • Apoptosis
  • Caspases/metabolism*
  • Cell Survival/physiology*
  • Cells, Cultured
  • Endothelium, Vascular/cytology*
  • Endothelium, Vascular/metabolism
  • Humans
  • Neuropilin-1/physiology*
  • Tumor Suppressor Protein p53/physiology*
  • Vascular Endothelial Growth Factor A/physiology
  • Vascular Endothelial Growth Factor Receptor-2/physiology
PubMed: 18000534 Full text @ PLoS One
Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), one of the crucial pro-angiogenic factors, functions as a potent inhibitor of endothelial cell (EC) apoptosis. Previous progress has been made towards delineating the VPF/VEGF survival signaling downstream of the activation of VEGFR-2. Here, we seek to define the function of NRP-1 in VPF/VEGF-induced survival signaling in EC and to elucidate the concomitant molecular signaling events that are pivotal for our understanding of the signaling of VPF/VEGF. Utilizing two different in vitro cell culture systems and an in vivo zebrafish model, we demonstrate that NRP-1 mediates VPF/VEGF-induced EC survival independent of VEGFR-2. Furthermore, we show here a novel mechanism for NRP-1-specific control of the anti-apoptotic pathway in EC through involvement of the NRP-1-interacting protein (NIP/GIPC) in the activation of PI-3K/Akt and subsequent inactivation of p53 pathways and FoxOs, as well as activation of p21. This study, by elucidating the mechanisms that govern VPF/VEGF-induced EC survival signaling via NRP-1, contributes to a better understanding of molecular mechanisms of cardiovascular development and disease and widens the possibilities for better therapeutic targets.