Basic FGF treatment of endothelial cells down-regulates the 85-KDa TGF beta receptor subtype and decreases the growth inhibitory response to TGF-beta 1.
Transforming growth factor-beta 1 (TGF beta 1) and basic fibroblast growth factor (bFGF) are known to be potent inhibitors and stimulators, respectively, of endothelial cell growth in vitro. In the present study we examined the effect of bFGF on endothelial cell growth inhibitory activity of TGF beta 1 and on the binding of (125I)-TGF beta 1 to these cells. The concentration of TGF beta 1 required for half-maximal inhibition of endothelial cell growth was increased in a dose-dependent manner by bFGF (a 20-100 fold increase at 1 ng/ml of bFGF). A 24 h-pretreatment of cells with bFGF resulted in abolition of the TGF beta 1 inhibitory effect on DNA synthesis. Moreover, the binding of (125I)-TGF beta 1 to the endothelial cell surface was decreased in a concentration-dependent and time-dependent manner after a preincubation of these cells with bFGF. Analysis of the binding parameters showed that bFGF decreased by two-fold the number of TGF beta receptors (to approximately 6000 receptors per cell). Cross-linking experiments with disuccinimidyl suberate demonstrated the presence of two TGF beta receptor subtypes, a predominant 85 kDa form and a minor 65 kDa form. Basic FGF decreased selectively the labeling of the 85 kDa TGF beta receptor subtype. These findings suggest that the growth stimulator bFGF can attenuate the cell's response to the growth inhibitor TGF beta 1.
Fafeur
V
V
Medical Research Division, American Cyanamid, Pearl River, NY 10965.
Terman
B I
BI
Blum
J
J
Böhlen
P
P
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta; D013388:Succinimides / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D013388:Succinimides; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004247:DNA; C019358:disuccinimidyl suberate