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Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay
Published on: June 30, 2023
CREG promotes vasculogenesis by activation of VEGF/PI3K/Akt pathway
Xiaoxiang Tian1, Na Zhang1, Chenghui Yan1
1Department of Cardiology, Shenyang Northern Hospital, 83 Wenhua Road, Shenyang, Liaoning 110840 China.
Insights
Cellular repressor of E1A-stimulated gene (CREG) promotes blood vessel formation (vasculogenesis) by up-regulating vascular endothelial growth factor (VEGF) and activating the PI3K/Akt pathway. This finding reveals CREG as a key regulator in endothelial cell development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Biology
Background:
- Vasculogenesis, the formation of new blood vessels, is crucial for development and disease.
- Factors regulating vasculogenesis are not fully understood.
- Cellular repressor of E1A-stimulated gene (CREG) is implicated in cellular differentiation and endothelial homeostasis.
Purpose of the Study:
- To investigate the role of CREG in regulating vasculogenesis.
- To elucidate the molecular mechanisms underlying CREG's function in blood vessel formation.
Main Methods:
- Utilized mouse embryonic stem cells (ESC) and embryoid body (EB) model.
- Manipulated CREG expression via overexpression and knockdown.
- Assessed EB formation, endothelial differentiation, and vasculogenesis.
- Analyzed expression of VEGF and activation of the PI3K/Akt pathway.
- Employed VEGF neutralizing antibodies and PI3K/Akt inhibitors.
Main Results:
- CREG expression increased during EB differentiation.
- CREG overexpression enhanced EB formation, endothelial differentiation, and vasculogenesis.
- CREG knockdown inhibited these processes.
- CREG influenced VEGF expression and PI3K/Akt pathway activation.
- VEGF and PI3K/Akt pathway were essential for CREG-mediated vasculogenesis.
Conclusions:
- CREG is a novel regulator of endothelial differentiation and vasculogenesis.
- CREG functions via the VEGF/PI3K/Akt signaling pathway.
- Targeting CREG may offer therapeutic potential for vascular diseases.
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.
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