IMR Press / FBL / Volume 19 / Issue 8 / DOI: 10.2741/4277

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
CREG promotes vasculogenesis by activation of VEGF/PI3K/Akt pathway
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1 Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China
2 Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA 19140 USA
3 Department of Surgery, Rutgers University Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 0809
Academic Editor:Xiao-Feng Yang
Front. Biosci. (Landmark Ed) 2014, 19(8), 1215–1226; https://doi.org/10.2741/4277
Published: 1 June 2014
(This article belongs to the Special Issue CREG promotes vasculogenesis by activation of VEGFPI3KAkt 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.

Keywords
REG
Embryonic stem cells
Vasculogenesis
Differentiation
VEGF
Endothelial cells
Review
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