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
Department of Molecular Cell Biology, Cancer Genomics Centre, Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Hubrecht Institute, Utrecht, The Netherlands ; Center for Interdisciplinary Research in Biology (CIRB), CNRS UMR 7241/INSERM U1050, Collège de France, Paris, France.
PLoS One. 2014 Jan 28;9(1):e86273. doi: 10.1371/journal.pone.0086273. eCollection 2014.
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.
内皮糖蛋白（ENG）是转化生长因子-β（TGF-β）家族成员的共受体，在内皮细胞中高度表达，在血管系统发育中起关键作用。ENG突变与称为遗传性出血性毛细血管扩张症1型的血管疾病相关。利用小鼠胚胎干细胞，我们观察到血管生成因子，包括血管内皮生长因子（VEGF），即使使用ENG缺陷细胞或使用短发夹RNA（shRNA）耗尽ENG的细胞，也能在胚状体中诱导血管生成。然而，干细胞衍生的内皮细胞有效组织成管状结构需要ENG。与这一发现一致，从E17.5 ENG杂合小鼠胚胎分离的胎儿跖骨显示VEGF诱导的血管网络形成减少。此外，shRNA介导的ENG耗尽和人脐静脉细胞中ENG的药理学抑制减轻了VEGF诱导的血管生成。总之，我们证明有效VEGF诱导的血管生成需要ENG。
