Insulin-like growth factor (IGF)-binding proteins inhibit the smooth muscle cell migration responses to IGF-I and IGF-II.

Abstract

Smooth muscle cells have been shown to migrate in response to insulin-like growth factor I (IGF-I). However, the role of IGF-binding proteins (IGFBPs) in this process has not been determined. As IGFBPs are synthesized and secreted by smooth muscle cells and bind to IGFs with high affinity, this study was undertaken to determine the ability of IGFBP-1 and -2 to modulate cellular migration in response to IGF-I and -II. Confluent monolayers of porcine vascular smooth muscle cells were wounded with a razor blade. After wounding, IGF-I and -II induced increases of 159 +/- 49% (mean +/- SD) and 108 +/- 33%, respectively, above control values in the number of cells migrating over a fixed distance in 4 days. The addition of IGFBP-1 caused a 19-21% inhibition of IGF-I- or IGF-II-stimulated migration, whereas the addition of IGFBP-2 inhibited the effect of both by greater than 60%. The addition of IGFBP-2 alone had no effect, whereas IGFBP-1 addition was associated with a 42 +/- 12% increase. In contrast, [Trp221]IGFBP-1 in which the RGD sequence was changed to WGD, thus eliminating its capacity to bind to the alpha 5 beta 1 integrin, inhibited IGF-I-stimulated migration by 67 +/- 17%. An IGF analog that has a reduced affinity for IGFBP-2-stimulated migration equally well as IGF-I alone even in the presence of IGFBP-2. Likewise, the addition of insulin, which cannot bind to IGFBPs, at supraphysiological concentrations that are adequate to activate the IGF-I receptor resulted in a similar increase in migration. In summary, IGF-I and -II stimulate smooth muscle cell migration after wounding. This migratory response is modulated by IGFBPs. Both IGFBP-1 and IGFBP-2 appear to neutralize the effects of the IGFs by inhibiting their interaction with IGF receptors, but IGFBP-1 also has a direct stimulatory effect that requires an intact RGD integrin recognition sequence.

Effect of trenbolone acetate plus estradiol on transcriptional regulation of metabolism pathways in bovine liver

“…IGF-1 and IGF-2 have been shown to stimulate the migration and proliferation of smooth muscle cells, whereas IGF-1 is more potent in the postnatal phase than IGF-2 in the prenatal phase (33,34). This response can be modulated by binding of IGF to IGFBP.…”

Insulin-Like Growth Factor-I Signaling in Smooth Muscle Cells Is Regulated by Ligand Binding to the 177CYDMKTTC184 Sequence of the β3-Subunit of αVβ3

“…pSMCs were isolated and maintained as previously described (20) Generation and Purification of the C177-C184 ␤3 Antibody (C-Loop ␤3 Antibody)…”

Effects of IGFBP-2 overexpression in vitro and in vivo

“…Either negative [24,27,28,29] or positive effects [30,31] have been observed after addition of exogenous IGFBP-2 to various cell systems. Impairment of cell growth by retinoic acid [32,33,34] or dexamethasone [35] was accompanied by increased IGFBP-2 expression, suggesting that IGFBP-2 may be involved in growth inhibition.…”