Premium
Upregulation of placental growth factor by vascular endothelial growth factor via a post‐transcriptional mechanism
Author(s) -
Yao Yong-Gang,
Yang Hoseong S.,
Cao Zhiming,
Danielsson Jennifer,
Duh Elia J.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.01.017
Subject(s) - vascular endothelial growth factor , downregulation and upregulation , placental growth factor , angiogenesis , umbilical vein , protein kinase c , vascular endothelial growth factor a , growth factor , vascular endothelial growth factor b , endocrinology , medicine , microbiology and biotechnology , biology , signal transduction , cancer research , receptor , biochemistry , vegf receptors , in vitro , gene
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.