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ENDOGLIN Is Dispensable for Vasculogenesis, but Required for Vascular Endothelial Growth Factor-Induced Angiogenesis

Lookup NU author(s): Professor Helen ArthurORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

ENDOGLIN (ENG) is a co-receptor for transforming growth factor-beta (TGF-beta) family members that is highly expressed in endothelial cells and has a critical function in the development of the vascular system. Mutations in Eng are associated with the vascular disease known as hereditary hemorrhagic telangiectasia type l. Using mouse embryonic stem cells we observed that angiogenic factors, including vascular endothelial growth factor (VEGF), induce vasculogenesis in embryoid bodies even when Eng deficient cells or cells depleted of Eng using shRNA are used. However, ENG is required for the stem cell-derived endothelial cells to organize effectively into tubular structures. Consistent with this finding, fetal metatarsals isolated from E17.5 Eng heterozygous mouse embryos showed reduced VEGF-induced vascular network formation. Moreover, shRNA-mediated depletion and pharmacological inhibition of ENG in human umbilical vein cells mitigated VEGF-induced angiogenesis. In summary, we demonstrate that ENG is required for efficient VEGF-induced angiogenesis.


Publication metadata

Author(s): Liu Z, Lebrin F, Maring JA, van den Driesche S, van der Brink S, van Dinther M, Thorikay M, Martin S, Kobayashi K, Hawinkels LJAC, van Meeteren LA, Pardali E, Korving J, Letarte M, Arthur HM, Theuer C, Goumans MJ, Mummery C, ten Dijke P

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2014

Volume: 9

Issue: 1

Print publication date: 28/01/2014

Acceptance date: 10/12/2013

Date deposited: 15/04/2014

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0086273

DOI: 10.1371/journal.pone.0086273

Notes: ARTN e86273


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Funding

Funder referenceFunder name
Royal Netherlands Academy of Arts and Sciences
Centre for Biomedical Genetics
Leducq Foundation
Netherlands Institute for Regenerative Medicine (NIRM)
UL2011-5051Dutch Cancer Society

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