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.

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