ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis

Zhen Liu; Franck Lebrin; Janita A Maring; Sander van den Driesche; Stieneke van der Brink; Maarten van Dinther; Midory Thorikay; Sabrina Martin; Kazuki Kobayashi; Lukas J A C Hawinkels; Laurens A van Meeteren; Evangelia Pardali; Jeroen Korving; Michelle Letarte; Helen M Arthur; Charles Theuer; Marie-José Goumans; Christine Mummery; Peter ten Dijke

doi:10.1371/journal.pone.0086273

ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis

Zhen Liu, Franck Lebrin, Janita A Maring, Sander van den Driesche, Stieneke van der Brink, Maarten van Dinther, Midory Thorikay, Sabrina Martin, Kazuki Kobayashi, Lukas J A C Hawinkels, Laurens A van Meeteren, Evangelia Pardali, Jeroen Korving, Michelle Letarte, Helen M Arthur, Charles Theuer, Marie-José Goumans, Christine Mummery, Peter ten Dijke

Research output: Contribution to journal › Article › peer-review

Abstract

ENDOGLIN (ENG) is a co-receptor for transforming growth factor-β (TGF-β) 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.

Original language	English
Pages (from-to)	e86273
Journal	PLoS ONE
Volume	9
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0086273
Publication status	Published - 28 Jan 2014

Keywords

Animals
Cell Differentiation
Flow Cytometry
Fluorescent Antibody Technique
Human Umbilical Vein Endothelial Cells
Humans
Intracellular Signaling Peptides and Proteins
Mice
Neovascularization, Physiologic
Vascular Endothelial Growth Factor A

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10.1371/journal.pone.0086273

ENDOGLIN Is Dispensable for Vasculogenesis, but Required for Vascular Endothelial Growth Factor-Induced Angiogenesis
Copyright: © 2014 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Liu, Z., Lebrin, F., Maring, J. A., van den Driesche, S., van der Brink, S., van Dinther, M., Thorikay, M., Martin, S., Kobayashi, K., Hawinkels, L. J. A. C., van Meeteren, L. A., Pardali, E., Korving, J., Letarte, M., Arthur, H. M., Theuer, C., Goumans, M-J., Mummery, C., & ten Dijke, P. (2014). ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis. PLoS ONE, 9(1), e86273. https://doi.org/10.1371/journal.pone.0086273

Liu, Zhen ; Lebrin, Franck ; Maring, Janita A ; van den Driesche, Sander ; van der Brink, Stieneke ; van Dinther, Maarten ; Thorikay, Midory ; Martin, Sabrina ; Kobayashi, Kazuki ; Hawinkels, Lukas J A C ; van Meeteren, Laurens A ; Pardali, Evangelia ; Korving, Jeroen ; Letarte, Michelle ; Arthur, Helen M ; Theuer, Charles ; Goumans, Marie-José ; Mummery, Christine ; ten Dijke, Peter. / ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis. In: PLoS ONE. 2014 ; Vol. 9, No. 1. pp. e86273.

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title = "ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis",

abstract = "ENDOGLIN (ENG) is a co-receptor for transforming growth factor-β (TGF-β) 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.",

keywords = "Animals, Cell Differentiation, Flow Cytometry, Fluorescent Antibody Technique, Human Umbilical Vein Endothelial Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A",

author = "Zhen Liu and Franck Lebrin and Maring, {Janita A} and {van den Driesche}, Sander and {van der Brink}, Stieneke and {van Dinther}, Maarten and Midory Thorikay and Sabrina Martin and Kazuki Kobayashi and Hawinkels, {Lukas J A C} and {van Meeteren}, {Laurens A} and Evangelia Pardali and Jeroen Korving and Michelle Letarte and Arthur, {Helen M} and Charles Theuer and Marie-Jos{\'e} Goumans and Christine Mummery and {ten Dijke}, Peter",

year = "2014",

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doi = "10.1371/journal.pone.0086273",

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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, M-J, Mummery, C & ten Dijke, P 2014, 'ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis', PLoS ONE, vol. 9, no. 1, pp. e86273. https://doi.org/10.1371/journal.pone.0086273

ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis. / Liu, Zhen; Lebrin, Franck; Maring, Janita A; van den Driesche, Sander; van der Brink, Stieneke; van Dinther, Maarten; Thorikay, Midory; Martin, Sabrina; Kobayashi, Kazuki; Hawinkels, Lukas J A C; van Meeteren, Laurens A; Pardali, Evangelia; Korving, Jeroen; Letarte, Michelle; Arthur, Helen M; Theuer, Charles; Goumans, Marie-José; Mummery, Christine; ten Dijke, Peter.

In: PLoS ONE, Vol. 9, No. 1, 28.01.2014, p. e86273.

Research output: Contribution to journal › Article › peer-review

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AU - Liu, Zhen

AU - Lebrin, Franck

AU - Maring, Janita A

AU - van den Driesche, Sander

AU - van der Brink, Stieneke

AU - van Dinther, Maarten

AU - Thorikay, Midory

AU - Martin, Sabrina

AU - Kobayashi, Kazuki

AU - Hawinkels, Lukas J A C

AU - van Meeteren, Laurens A

AU - Pardali, Evangelia

AU - Korving, Jeroen

AU - Letarte, Michelle

AU - Arthur, Helen M

AU - Theuer, Charles

AU - Goumans, Marie-José

AU - Mummery, Christine

AU - ten Dijke, Peter

PY - 2014/1/28

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N2 - ENDOGLIN (ENG) is a co-receptor for transforming growth factor-β (TGF-β) 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.

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KW - Animals

KW - Cell Differentiation

KW - Flow Cytometry

KW - Fluorescent Antibody Technique

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Mice

KW - Neovascularization, Physiologic

KW - Vascular Endothelial Growth Factor A

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