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

Ling Wang, Shamit K. Dutta, Tatsuyoshi Kojima, Xiaolei Xu, Roya Khosravi-Far, Stephen C. Ekker, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Article numbere1161
JournalPloS one
Volume2
Issue number11
DOIs
StatePublished - Nov 14 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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