Interaction of Receptors for Insulin-Like Growth Factor I, Platelet-Derived Growth Factor, and Fibroblast Growth Factor in Rat Aortic Cells

Abstract

Serum contains various growth factors which regulate the proliferation of cells. We investigated the growth of cultured arterial smooth muscle cells under the influence of insulin-like growth factor I (IGF I), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), and examined the effect of these growth factors on the binding of [125I] IGF I and on the binding of [125I]PDGF to these cells. IGF I, FGF, and PDGF stimulated [6-3H]thymidine incorporation into DNA of confluent cultures of cells which were incubated in modified Dulbecco's modified Eagle medium. However, the effect of these growth factors on DNA synthesis was much more potent in Dulbecco's modified Eagle medium with 1% fetal calf serum. FGF and PDGF potentiated the growth-promoting effect of IGF I. The binding of [125I]IGF I to the cells was increased after a preincubation with FGF and PDGF. The binding was potently increased by FGF (100 ng/ml) after a preincubation time of 30 min. There was an increase in binding during the first 3 h of preincubation followed by a decrease after 4-5 h. PDGF (10-1000 ng/ml) stimulated [125I]IGF I binding only after 2 h of preincubation. The stimulation was dose dependent. Maximal stimulation of the binding was observed after 3 h of preincubation followed by a decrease after 4-5 h of preincubation. Specific binding sites for PDGF on smooth muscle cells could be demonstrated too. A preincubation of confluent cells with IGF I caused a dose-dependent increase in [125I]PDGF binding. These results support the hypothesis that the regulation of the binding of a specific growth factor by a second growth factor is important for the control of cell growth.

G-protein coupled and tyrosine kinase receptors: evidence that activation of the insulin-like growth factor I receptor is required for thrombin-induced mitogenesis of rat aortic smooth muscle cells.

“…Thus, both PDGF and angiotensin II upregulate IGF I receptors on VSMC (40,41) and their mitogenic effects are blocked by anti-IGF I antiserum (6,14). The concept that upregulation of IGF I receptors may serve a key function in mitogenic responses to agonists is supported by our recent demonstration that VSMC mitogenic responses to angiotensin II are almost completely inhibited by downregulation of IGF I receptors (31).…”

Translation Initiation of the Insulin-like Growth Factor I Receptor mRNA Is Mediated by an Internal Ribosome Entry Site

“…The IGF-IR plays a central role during the cell cycle, as demonstrated by the fact that overexpression of IGF-IR abrogates requirements for exogenous growth factors (4). In vascular smooth muscle cells (VSMCs),the IGF-IR mediates the mitogenic effects of various growth factors such as platelet-derived growth factor, endothelial growth factor, fibroblast growth factor ␤, thrombin, and angiotensin II, consistent with an important role in cardiovascular growth responses (5)(6)(7)(8). A variety of studies have shown that relatively small changes in IGF-IR expression have important proliferative or antiproliferative effects (9 -11).…”

Differential Regulation of Insulin-like Growth Factor-I (IGF-I) Receptor Gene Expression by IGF-I and Basic Fibroblastic Growth Factor

“…Both bFGF and PDGF synergize with IGF-I in their biological actions (25,26). The results of the present study suggest that one mechanism may be the increased expression of the IGF-I receptor by these growth factors.…”