Hypoxia-induced transcriptional activation of vascular endothelial growth factor is inhibited by serum.
Expression of vascular endothelial growth factor (VEGF) by cultured vascular smooth muscle cells was analyzed. Serum and hypoxia had nearly additive actions on VEGF mRNA expression. The function of the VEGF promoter in smooth muscle cells was analyzed using transient luciferase reporter assays. Serum and hypoxia stimulated expression of luciferase. The presence of hypoxia response element (HRE) was necessary for the hypoxic induction. AP-1 sequences located upstream of HRE and AP-2/Sp-1 sequences located downstream of HRE are not necessary. Hypoxic responses were best observed in serum-deprived cells. They were largely absent in serum-stimulated cells. Serum did not suppress the hypoxic response by interfering with the hypoxia sensor mechanism or with the signaling cascade that leads to the activation of HIF-1. It is concluded that growth-promoting cytokines regulate hypoxic gene induction in smooth muscle cells.
D'Angelo
G
G
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia-Antipolis, Valbonne, 06560, France. dangelo@ipmc.cnrs.fr
Ladoux
A
A
Frelin
C
C
D000818:Animals; D001011:Aorta; D001769:Blood; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D003470:Culture Media; D016228:Endothelial Growth Factors / Q000235:genetics*; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D008222:Lymphokines / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D003470:Culture Media; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D008156:Luciferases