title: CREG promotes vasculogenesis by activation of VEGF/PI3K/Akt pathway.
abstract: Knowledge about factors regulating vasculogenesis remains limited. The cellular repressor of E1A-stimulated gene (CREG) has been reported to be involved in maintaining cellular differentiation and endothelial homeostasis, thus we hypothesize that CREG may be a novel factor regulating vasculogenesis. By using mouse embryonic stem cells (ESC) derived embryoid body (EB) model, we confirmed expression of CREG was significantly up-regulated during EB differentiation. Overexpression of CREG in ESC led to accelerated cystic EB formation, increased endothelial differentiation and vasculogenesis, whereas knockdown of CREG produced opposite phenotypes. Moreover, we found expression of vascular endothelial growth factor (VEGF) was up-regulated and PI3K/Akt pathway was activated in CREG-overexpressing EB. Administration of VEGF neutralizing antibody or PI3K/Akt pharmacological inhibitor LY294002 blocked the vasculogenesis in CREG over-expressing EB, while supplement of VEGF rescued vasculogenesis deficiency in CREG knocked down EB. Further study by Western blot determined that PI3K/Akt was a downstream effector of VEGF. We identify CREG as a novel factor in regulating endothelial differentiation and vasculogenesis via VEGF/PI3K/Akt pathway.
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Jun
authors.initials: J
authors.lastname: Nelsen
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Chengfei
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C485248:Creg protein, mouse; D012097:Repressor Proteins; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt