title: Cellular repressor of E1A-stimulated genes regulates vascular endothelial cell migration by the ILK/AKT/mTOR/VEGF(165) signaling pathway.
abstract: The migration of vascular endothelial cells plays a critical role in a variety of vascular physiological and pathological processes, such as embryonic development, angiogenesis, wound healing, re-endothelialization, and vascular remodeling. This study clarified the role and mechanism of a new vascular homeostasis regulator, Cellular repressor of E1A-stimulated genes (CREG), in the migration of primary human umbilical vein endothelial cells (HUVECs). A wound healing assay and transwell migration model showed that upregulation of CREG expression induced HUVEC migration and it was positively correlated with the expression of vascular endothelial growth factor. Furthermore, wild type integrin-linked kinase reversed the poor mobility of CREG knock-down HUVECs; in contrast, kinase-dead integrin-linked kinase weakened the migration of HUVECs. We also studied the effect of CREG on HUVEC migration by the addition of an mTOR inhibitor, recombinant vascular endothelial growth factor(165), neutralizing antibody of vascular endothelial growth factor(165) and AKT siRNA, and we concluded that CREG induces endothelial cell migration by activating the integrin-linked kinase/AKT/mTOR/VEGF(165) signaling pathway.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Tao
authors.forename: Shaowei
authors.initials: S
authors.lastname: Liu
authors.forename: Chenghui
authors.initials: C
authors.lastname: Yan
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
mesh_terms: D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D012097:Repressor Proteins; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D000099200:Scaffold Protein ILK; C114068:CREG1 protein, human; C467484:VEGFA protein, human; C546842:MTOR protein, human