Platelet-derived Growth Factor Production by Human Umbilical Vein Endothelial Cells is Regulated by Basic Fibroblast Growth Factor

Human umbilical vein endothelial cells express the B chain gene (c-sis) of platelet-derived growth factor (PDGF). PDGF acts as a mitogen for mesenchymal cells and has recently been reported to be a potent vasoconstrictor (Berk, B. C., Alexander, R. W., Brock, T. A., Gimbrone, M. A., Jr., and Webb, R. C. (1986) Science 232, 87-90). Regulation of c-sis therefore, may play an important role in maintaining and controlling the integrity of the vasculature. We report here that basic fibroblast growth factor (bFGF), a growth factor for endothelial cells in culture, significantly decreases the amount of PDGF-like protein secreted by these cells. Levels of c-sis mRNA increase more than 10-fold in the absence of bFGF. This effect is specific for the B chain of PDGF as transcript levels of other growth factors synthesized by endothelial cells, such as transforming growth factor beta are not affected by bFGF. c-sis mRNA levels increase 12 h after bFGF removal as the cells begin to accumulate in G0 stage of the cell cycle and remain elevated for at least 96 h. Transcript levels fall again upon re-exposure of the cells to bFGF. bFGF may regulate c-sis mRNA levels and PDGF protein production by endothelial cells either directly, or indirectly via cell cycle arrest at G0. This effect is not due to nonspecific cessation of cell growth because arresting the cells at S phase or in metaphase does not result in increased c-sis transcript levels.