期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 19, 期 -, 页码 1215-1226出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4277
关键词
REG; Embryonic stem cells; Vasculogenesis; Differentiation; VEGF; Endothelial cells; Review
资金
- National Natural Science Foundation of China [81130072, 81370143]
- National Science and Technology Major Project of China [2012ZX09303016-002]
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.
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