%0 Journal Article
%T Neuropilin-1 Modulates p53/Caspases Axis to Promote Endothelial Cell Survival
%A Ling Wang
%A Shamit K. Dutta
%A Tatsuyoshi Kojima
%A Xiaolei Xu
%A Roya Khosravi-Far
%A Stephen C. Ekker
%A Debabrata Mukhopadhyay
%J PLOS ONE
%D 2007
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0001161
%X 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001161