Insulin-like growth factor (IGF)-binding proteins inhibit the smooth muscle cell migration responses to @entity442 and XXXX .

@entity31772 @entity12067 @entity442 @entity10116 @entity10513 @entity5100 @entity2856
Smooth muscle cells have been shown to migrate in response to @entity442 ( @entity442 ). 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 @entity31772 to modulate cellular migration in response to @entity12067 . Confluent monolayers of porcine vascular smooth muscle cells were wounded with a razor blade. After wounding, @entity12067 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 @entity10116 caused a 19-21% inhibition of @entity442 - or @entity5100 -stimulated migration, whereas the addition of @entity10513 inhibited the effect of both by greater than 60%. The addition of @entity10513 alone had no effect, whereas @entity10116 addition was associated with a 42 +/- 12% increase. In contrast, [Trp221] @entity10116 in which the RGD sequence was changed to WGD, thus eliminating its capacity to bind to the alpha 5 beta 1 integrin, inhibited @entity442 -stimulated migration by 67 +/- 17%. An IGF analog that has a reduced affinity for @entity10513 -stimulated migration equally well as @entity442 alone even in the presence of @entity10513 . Likewise, the addition of insulin, which cannot bind to IGFBPs, at supraphysiological concentrations that are adequate to activate the @entity2856 resulted in a similar increase in migration. In summary, @entity12067 stimulate smooth muscle cell migration after wounding. This migratory response is modulated by IGFBPs. Both @entity10116 and @entity10513 appear to neutralize the effects of the IGFs by inhibiting their interaction with IGF receptors, but @entity10116 also has a direct stimulatory effect that requires an intact RGD integrin recognition sequence.
