Neuropilin-1 modulates p53/caspases axis to promote endothelial cell survival

61Citations
Citations of this article
42Readers
Mendeley users who have this article in their library.

Abstract

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-incluced 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. © 2007 Wang et al.

Cite

CITATION STYLE

APA

Wang, L., Dutta, S. K., Kojima, T., Xu, X., Khosravi-Far, R., Ekker, S. C., & Mukhopadhyay, D. (2007). Neuropilin-1 modulates p53/caspases axis to promote endothelial cell survival. PLoS ONE, 2(11). https://doi.org/10.1371/journal.pone.0001161

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free