Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability.
Vessel growth is often associated with ischemia. VEGF, a potent angiogenic factor, has been shown to be induced by low oxygen concentrations. These studies were conducted to investigate the molecular basis of the hypoxia-induced increase in VEGF mRNA. Run-on analysis of VEGF revealed a minimal increase in the rate of gene transcription in a human retinal epithelial cell line grown under hypoxic conditions. Examination of VEGF mRNA stability revealed that the half-life of VEGF transcripts under normoxia was short, 30-45 min, but was dramatically increased to 6-8 h in cells grown under hypoxia. Cobalt chloride, which elevates VEGF and has been suggested to be similar to hypoxia in its mechanism of action, had only a slight effect on decay rate. We postulate that hypoxia-induced increases in mRNA stability provide the sustained increases in VEGF mRNA levels necessary to support a neovascular response.
Shima
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Program in Biological and Biomedical Sciences, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA.
Deutsch
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U
D'Amore
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PA
D002478:Cells, Cultured; D004355:Drug Stability; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry*; D012160:Retina / Q000648:ultrastructure; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors