Bifunctional effects of transforming growth factor-beta (TGF-beta) on endothelial cell growth correlate with phenotypes of TGF-beta binding sites.
Transforming growth factor-beta (TGF-beta) is a bifunctional, dose-dependent regulator of endothelial cell proliferation induced in vitro by heparin-binding growth factor 1 (HBGF-1, acidic FGF). Here we have examined the relationship between endothelial cell growth and the expression of cell surface binding sites for TGF-beta and HBGF-1. Fetal bovine heart endothelial cell (FBHEC) growth was stimulated by low concentrations of TGF-beta and inhibited by high concentrations of TGF-beta while expressing two distinct classes of TGF-beta binding sites with binding constants of 24 pM (6300 sites/cell) and 900 pM (12,000 sites/cell). In contrast, human umbilical vein endothelial cells (HUVEC), whose growth was slightly promoted by TGF-beta, exhibited a single class of high-affinity TGF-beta binding sites (Kd = 45 pM, 4500 sites/cell). Affinity crosslinking using [125I]TGF-beta showed that FBHEC expressed two distinct low molecular weight TGF-beta binding sites (Mr 85,000 and 58,000), while HUVEC expressed a single type of low molecular weight TGF-beta binding site (Mr 85,000). As detected by binding of [125I]HBGF-1, preincubation of FBHEC with high concentrations of TGF-beta transmodulated the expression of high-affinity HBGF-1 receptors. In contrast, no transmodulation of HBGF-1 receptors occurred in FBHEC during preincubation with low concentrations of TGF-beta. Furthermore, preincubation of HUVEC with TGF-beta did not transmodulate the expression of HBGF-1 receptors. The data suggest that the ability of TGF-beta to stimulate or inhibit endothelial cell proliferation in a dose-dependent manner correlated with the expression of specific TGF-beta binding site subtypes and involved the transmodulation of HBGF-1 receptors.
Myoken
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W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946.
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Sato
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McKeehan
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Sato
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D000818:Animals; D001665:Binding Sites / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor; D011975:Receptors, Mitogen / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D040262:Receptors, Vascular Endothelial Growth Factor; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011975:Receptors, Mitogen; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016220:Fibroblast Growth Factor 1; D040262:Receptors, Vascular Endothelial Growth Factor