Laboratory of Molecular Biology , Jerome H. Holland Laboratory for the Biomedical Sciences , American Red Cross , Rockville , Maryland 20855 .
J Biol Chem 265 : 3284-92 ( 1990)
Abstract
Heparin-binding growth factor-1 ( HBGF-1 ) , also known as acidic fibroblast growth factor , is a potent mitogen for a variety of cell types including vascular endothelial and smooth muscle cells .
Studies using murine 3T3 fibroblasts have shown that HBGF-1 induces numerous cellular responses such as the tyrosine phosphorylation of specific polypeptides and the increased expression of actin mRNA .
Here we report that the addition of HBGF-1 to quiescent human umbilical vein endothelial cells increases the level of platelet-derived growth factor ( PDGF ) A-chain mRNA but not PDGF B-chain mRNA .
In contrast , factors that inhibit endothelial cell proliferation such as phorbol myristate acetate and the cytokines interleukin-1 , interleukin-6 , and tumor necrosis factor-alpha increase both PDGF A-chain and B-chain mRNA levels .
HBGF-1 induction of PDGF A-chain mRNA expression occurs in the presence of the protein synthesis inhibitor cycloheximide and thus does not require de novo protein synthesis .
HBGF-1 also increases c-fos , c-jun , and c-myc mRNA levels ; in the presence of cycloheximide , PDGF A-chain and protooncogene mRNA accumulation kinetics are similar .
Nuclear run-on experiments indicate that the transcription rate of the PDGF A-chain gene transiently increases after HBGF-1 addition .
Immunoprecipitation analysis using PDGF A-chain-specific antibodies indicates that HBGF-1-stimulated cells synthesize and secrete an increased amount of PDGF relative to unstimulated cells .
If HBGF-1 can regulate PDGF expression by vascular endothelial cells in vivo , then HBGF-1 availability would be an important component of smooth muscle cell growth control .
For example , HBGF-1 within the vessel wall would promote smooth muscle cell proliferation by ( a ) direct interaction with smooth muscle cell HBGF-1 receptors , and ( b ) increasing the amount of endothelial cell-derived PDGF available for binding to smooth muscle cell PDGF receptors .