Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability

FEBS Letters

D'Amore, Patricia A.¹  Shima, David T.¹  Deutsch, Urban² 

[1] Program in Biological and Biomedical Sciences, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA;Max Planck Institut fur physiologische und klinische Forschung, W-6350 Bad Nauhein, Germany

关键词: Post-transcriptional regulation;    Oxygen;    Angiogenesis;    Cobalt;    VEGF;    vascular endothelial growth factor;    hRPE;    human retinal pigment epithelial cells;    tRPE;    SV40 T antigen transformed human retinal pigment epithelial cells;   

DOI  :  10.1016/0014-5793(95)00831-S

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown