Bifunctional effects of transforming growth factor-β (TGF-β) on endothelial cell growth correlate with phenotypes of TGF-β binding sites

Abstract

Transforming growth factor-β (TGF-β) 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-β and HBGF-1. Fetal bovine heart endothelial cell (FBHEC) growth was stimulated by low concentrations of TGF-β and inhibited by high concentrations of TGF-β while expressing two distinct classes of TGF-β binding sites with binding constants of 24 p M (6300 sites/cell) and 900 p M (12,000 sites/cell). In contrast, human umbilical vein endothelial cells (HUVEC), whose growth was slightly promoted by TGF-β, exhibited a single class of high-affinity TGF-β binding sites ( K d = 45 p M, 4500 sites/cell). Affinity crosslinking using [ 125I]TGF-β showed that FBHEC expressed two distinct low molecular weight TGF-β binding sites ( M r 85,000 and 58,000), while HUVEC expressed a single type of low molecular weight TGF-β binding site ( M r 85,000). As detected by binding of [ 125I]HBGF-1, preincubation of FBHEC with high concentrations of TGF-β 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-β. Furthermore, preincubation of HUVEC with TGF-β did not transmodulate the expression of HBGF-1 receptors. The data suggest that the ability of TGF-β to stimulate or inhibit endothelial cell proliferation in a dose-dependent manner correlated with the expression of specific TGF-β binding site subtypes and involved the transmodulation of HBGF-1 receptors.