PMID- 7641334
OWN - NLM
STAT- MEDLINE
DCOM- 19950921
LR  - 20220330
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 77
IP  - 3
DP  - 1995 Sep
TI  - Hypoxia regulates vascular endothelial growth factor gene expression in 
      endothelial cells. Identification of a 5' enhancer.
PG  - 638-43
AB  - Vascular endothelial growth factor (VEGF) is a potent mitogen specific for 
      endothelial cells. Its expression is dramatically induced by low oxygen tension 
      in a variety of cell types, and it has been suggested to be a key mediator of 
      hypoxia-induced angiogenesis. Although VEGF action is targeted to endothelial 
      cells, it is generally believed that these cells do not express VEGF. In 
      addition, the mechanisms by which hypoxia regulates VEGF production remain 
      unclear. We report in the present study that pulmonary artery endothelial cells 
      do not express VEGF under basal conditions; however, significant VEGF mRNA levels 
      accumulate when these cells are exposed to hypoxia. Using a DNA fragment 
      containing human VEGF promoter sequence, we identified a 28-bp element that is 
      necessary and sufficient to upregulate transcription in response to hypoxia. This 
      element can act as a hypoxia-specific enhancer when placed upstream or downstream 
      from a heterologous promoter. The enhancer includes, in addition to an octamer 
      homologous to the hypoxia-inducible factor-1 (HIF-1) consensus, a sequence that 
      resides 3' to the consensus. Although this sequence may not be involved in the 
      binding of HIF-1, it is absolutely required for the enhancer activity and may be 
      the binding site for certain constitutive binding proteins. The expression of 
      VEGF by endothelial cells in response to hypoxia may provide an important 
      mechanism by which endothelial cell permeability and proliferation is regulated 
      in an autocrine manner.
FAU - Liu, Y
AU  - Liu Y
AD  - Joint Program in Neonatology, Harvard Medical School, Boston, Mass, USA.
FAU - Cox, S R
AU  - Cox SR
FAU - Morita, T
AU  - Morita T
FAU - Kourembanas, S
AU  - Kourembanas S
LA  - eng
GR  - HL-09008/HL/NHLBI NIH HHS/United States
GR  - P50 HL-46491/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cattle
MH  - *Cell Hypoxia
MH  - Cells, Cultured
MH  - Endothelial Growth Factors/*genetics
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - *Enhancer Elements, Genetic
MH  - *Gene Expression Regulation
MH  - Lymphokines/*genetics
MH  - Molecular Sequence Data
MH  - RNA, Messenger/analysis
MH  - Transcription, Genetic
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - 10.1161/01.res.77.3.638 [doi]
PST - ppublish
SO  - Circ Res. 1995 Sep;77(3):638-43. doi: 10.1161/01.res.77.3.638.