Upregulation of placental growth factor by vascular endothelial growth factor via a post-transcriptional mechanism

Yong Gang Yao, Hoseong S. Yang, Zhiming Cao, Jennifer Danielsson, Elia J. Duh

Research output: Contribution to journalArticlepeer-review

Abstract

Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are key angiogenic stimulators during normal development and wound healing, as well as in a variety of pathological conditions. Recent studies have demonstrated a synergistic effect of VEGF and PlGF in pathological angiogenesis and suggest a role for PlGF in amplifying VEGF action in endothelial cells. We show here in the mouse model of oxygen-induced retinopathy that VEGF is significantly increased (P < 0.01) in the retina at both the mRNA and protein levels. In this mouse model, PlGF was significantly upregulated in the retina at the protein level (P < 0.01) without a corresponding change in mRNA levels. In cultured human retinal and umbilical vein endothelial cells, VEGF induced the production of PlGF protein by over 10-fold (P < 0.01) in a dose-dependent manner through a post-transcriptional mechanism. The increased PlGF expression upon VEGF treatment was significantly reduced by inhibition of the protein kinase C (PKC) and MEK signaling pathways, as well as by treatment with the calcium ionophore A23187. Taken together, our findings demonstrate that VEGF can amplify its effects on endothelial cells by inducing the production of PlGF via a post-transcriptional mechanism in a PKC-dependent manner, and provide a potential link between PKC inhibition and amelioration of vascular complications in the development of angiogenic diseases.

Original languageEnglish (US)
Pages (from-to)1227-1234
Number of pages8
JournalFEBS Letters
Volume579
Issue number5
DOIs
StatePublished - Feb 14 2005

Keywords

  • Angiogenesis
  • Endothelial cell
  • Placental growth factor
  • Proliferative diabetic retinopathy
  • Protein kinase C
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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