Regulation of angiogenic growth factor expression by hypoxia, transition metals, and chelating agents

J. M. Gleadle, B. L. Ebert, J. D. Firth, P. J. Ratcliffe

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246 Citations (Scopus)


Recent work has indicated that oxygen-sensing mechanism(s) resembling those controlling erythropoietin production operate in many non- erythropoietin-producing cells. To pursue the implication that such a system might control other genes, we studied oxygen-regulated expression of mRNAs for vascular endothelial growth factor, platelet-derived growth factor (PDGF) A and B chains, placental growth factor (PLGF), and transforming growth factor in four different cell lines and compared the characteristics with those of erythropoietin regulation. Oxygen-regulated expression was demonstrated for each gene in at least one cell type. However, the response to hypoxia (1% oxygen) varied markedly, ranging from a 13-fold increase (PDGF-B in Hep G2 cells) to a 2-fold decrease (PLGF in the trophoblastic line BeWo). For each gene/cell combination, both the magnitude and direction of the response to hypoxia were mimicked by exposure to cobaltous ions or two different iron-chelating agents, desferrioxamine and hydroxypyridinones. These similarities with established characteristics of erythropoietin regulation indicate that a similar mechanism of oxygen sensing is operating on a variety of vascular growth factors, and they suggest that chelatable iron is closely involved in the mechanism.

Original languageEnglish
Pages (from-to)C1362-C1368
JournalAmerican Journal of Physiology - Cell Physiology
Issue number6
Publication statusPublished - Jun 1995
Externally publishedYes


  • cobalt
  • erythropoietin
  • iron
  • oxygen sensor


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