| RRC ID |
38776
|
| Author |
Nomura M, Yamagishi S, Harada S, Hayashi Y, Yamashima T, Yamashita J, Yamamoto H.
|
| Title |
Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes.
|
| Journal |
J Biol Chem
|
| Abstract |
Hypoxia is the principal factor that causes angiogenesis. These experiments were conducted to explore how it induces the proliferation of vascular cells, a key step in angiogenesis. Human umbilical vein endothelial cells and bovine retinal pericytes were grown in controlled atmosphere culture chambers containing various concentrations of oxygen. The numbers of both endothelial cells and pericytes increased significantly under hypoxic conditions; the O2 concentrations that achieved maximal growth promotion were 10% for endothelial cells and 2.5% for pericytes. Quantitative reverse transcription-polymerase chain reaction analysis revealed that mRNAs coding for the secretory forms of vascular endothelial growth factor (VEGF), a mitogen specific to endothelial cells, were present in both endothelial cells and pericytes and that their levels increased significantly in the two cell types as the atmospheric O2 concentration decreased. The two genes for VEGF receptors, kinase insert domain-containing receptor (kdr) and fms-like tyrosine kinase 1 (flt1), were found to be constitutively expressed in endothelial cells, and their relative mRNA levels were ranked in that order. On the other hand, only flt1 mRNA was detected in pericytes under hypoxic conditions. Furthermore, most antisense oligodeoxyribonucleotides complementary to VEGF mRNAs efficiently inhibited DNA synthesis in endothelial cells cultured under hypoxic conditions. These results indicate that autocrine and paracrine VEGFs may take part in the hypoxia-induced proliferation of endothelial cells.
|
| Volume |
270(47)
|
| Pages |
28316-24
|
| Published |
1995-11-24
|
| DOI |
10.1074/jbc.270.47.28316
|
| PII |
S0021-9258(18)87932-7
|
| PMID |
7499331
|
| MeSH |
Animals
Base Sequence
Cattle
Cell Division / drug effects
Cell Division / physiology
Cell Hypoxia
Cells, Cultured
DNA / antagonists & inhibitors
DNA / biosynthesis
DNA Primers
DNA Replication / drug effects
Endothelial Growth Factors / biosynthesis
Endothelial Growth Factors / physiology*
Endothelium, Vascular / cytology*
Endothelium, Vascular / drug effects
Endothelium, Vascular / physiology*
Humans
Kinetics
Lymphokines / biosynthesis
Lymphokines / physiology*
Microcirculation
Molecular Sequence Data
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / drug effects
Muscle, Smooth, Vascular / physiology*
Oligonucleotide Probes
Oligonucleotides, Antisense / pharmacology
Polymerase Chain Reaction
Proto-Oncogene Proteins / biosynthesis
RNA, Messenger / biosynthesis
Receptor Protein-Tyrosine Kinases / biosynthesis*
Receptors, Growth Factor / biosynthesis*
Receptors, Mitogen / biosynthesis
Receptors, Vascular Endothelial Growth Factor
Retina
Retinal Vessels
Umbilical Veins
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factors
|
| IF |
4.238
|
| Times Cited |
283
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
U251(RCB0461) |
