Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis

Lei Nie, Xiaojia Guo, Leila Esmailzadeh, Jiasheng Zhang, Abolfazl Asadi, Mark Collinge, Xuan Li, Jun Dae Kim, Melissa Woolls, Suk Won Jin, Alexandre Dubrac, Anne Eichmann, Michael Simons, Jeffrey R. Bender, Mehran M. Sadeghi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Aberrant blood vessel formation contributes to a wide variety of pathologies, and factors that regulate angiogenesis are attractive therapeutic targets. Endothelial and smooth muscle cell-derived neuropilin-like protein (ESDN) is a neuropilin-related transmembrane protein expressed in ECs; however, its potential effect on VEGF responses remains undefined. Here, we generated global and EC-specific Esdn knockout mice and demonstrated that ESDN promotes VEGF-induced human and murine EC proliferation and migration. Deletion of Esdn in the mouse interfered with adult and developmental angiogenesis, and knockdown of the Esdn homolog (dcbld2) in zebrafish impaired normal vascular development. Loss of ESDN in ECs blunted VEGF responses in vivo and attenuated VEGF-induced VEGFR-2 signaling without altering VEGF receptor or neuropilin expression. Finally, we found that ESDN associates with VEGFR-2 and regulates its complex formation with negative regulators of VEGF signaling, protein tyrosine phosphatases PTP1B and TC-PTP, and VEcadherin. These findings establish ESDN as a regulator of VEGF responses in ECs that acts through a mechanism distinct from neuropilins. As such, ESDN may serve as a therapeutic target for angiogenesis regulation.

Original languageEnglish (US)
Pages (from-to)5082-5097
Number of pages16
JournalJournal of Clinical Investigation
Volume123
Issue number12
DOIs
StatePublished - Dec 2 2013

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis'. Together they form a unique fingerprint.

Cite this