ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis.
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.
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Zhen
Z
Liu
Hubrecht Institute, Utrecht, The Netherlands ; Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241/INSERM U1050, Collège de France, Paris, France.
Franck
F
Lebrin
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Janita A
JA
Maring
Hubrecht Institute, Utrecht, The Netherlands.
Sander
S
van den Driesche
Hubrecht Institute, Utrecht, The Netherlands.
Stieneke
S
van der Brink
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Maarten
M
van Dinther
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Midory
M
Thorikay
Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241/INSERM U1050, Collège de France, Paris, France.
Sabrina
S
Martin
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Kazuki
K
Kobayashi
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Lukas J A C
LJ
Hawinkels
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Laurens A
LA
van Meeteren
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Evangelia
E
Pardali
Hubrecht Institute, Utrecht, The Netherlands.
Jeroen
J
Korving
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.
Michelle
M
Letarte
Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.
Helen M
HM
Arthur
Tracon Pharmaceuticals, San Diego, California, United States of America.
Charles
C
Theuer
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Marie-José
MJ
Goumans
Hubrecht Institute, Utrecht, The Netherlands ; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
Christine
C
Mummery
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Peter
P
ten Dijke
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D000071063:Endoglin; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A