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PLoS One. 2014 Jan 28;9(1):e86273. doi: 10.1371/journal.pone.0086273. eCollection 2014.

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

Author information

1
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
2
Hubrecht Institute, Utrecht, The Netherlands ; Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241/INSERM U1050, Collège de France, Paris, France.
3
Hubrecht Institute, Utrecht, The Netherlands.
4
Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241/INSERM U1050, Collège de France, Paris, France.
5
Molecular Structure and Function Program, The Hospital of Sick Children, Department of Immunology and Heart and Stroke Richard Lewar Center of Excellence, University of Toronto, Toronto, Ontario, Canada.
6
Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.
7
Tracon Pharmaceuticals, San Diego, California, United States of America.
8
Hubrecht Institute, Utrecht, The Netherlands ; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.

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.

PMID:
24489709
PMCID:
PMC3904881
DOI:
10.1371/journal.pone.0086273
[Indexed for MEDLINE]
Free PMC Article

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