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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 publication

DOI

10.1152/ajpcell.1995.268.6.C1362

Type

Journal article

Journal

Am J Physiol

Publication Date

06/1995

Volume

268

Pages

C1362 - C1368

Keywords

Angiogenesis Inducing Agents, Carcinoma, Hepatocellular, Cell Hypoxia, Cell Line, Chelating Agents, Cobalt, Deferoxamine, Endothelial Growth Factors, Erythropoietin, Gene Expression Regulation, Neoplastic, Growth Substances, Humans, Liver Neoplasms, Lymphokines, Molecular Sequence Data, Neovascularization, Pathologic, Placenta Growth Factor, Platelet-Derived Growth Factor, Pregnancy Proteins, RNA, Messenger, RNA, Small Nuclear, Transforming Growth Factor beta, Tumor Cells, Cultured, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors