Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I.

Abstract

Abstract. Insulin-like growth factor binding proteins (IGFBPs) have been shown to serve as carrier proteins for the insulin-like growth factors (IGFs) and to modulate their biologic effects. Since extracellular matrix (ECM) has been shown to be a reservoir for IGF-I and IGF-U, we examined the ECM of cultured human fetal fibroblasts and found that IGFBP-5 was incorporated intact into ECM, while mostly inert proteolytic fragments were found in the medium. In contrast, two other forms of IGFBP that are secreted by these cells were either present in ECM in minimal amounts (IGFBP-3) or not detected (IGFBP-4). Likewise, when purified IGFBPs were incubated with ECM, IGFBP-5 bound preferentially. IGFBP-5 was found to bind to types III and IV collagen, laminin, and fibronectin. Increasing salt concentrations inhibited the binding of IGFBP-5 to ECM and accelerated the release of IGFBP-5 from ECM, suggesting an ionic basis for this interaction. ECM-associated IGFBP-5 had a sevenfold decrease in affinity for IGF-I compared to IGFBP-5 in solution. Furthermore, when IGFBP-5 was present in cell culture substrata, it potentiated the growth stimulatory effects of IGF-I on fibroblasts. When IGFBP-5 was present only in the medium, it was degraded to a 22-kD fragment and had no effect on IGF-I-stimulated growth. We conclude that IGFBP-5 is present in fibroblast ECM, where it is protected from degradation and can potentiate the biologic actions of IGF-I. These findings provide a molecular explanation for the association of the IGF's with the extracellular matrix, and suggest that the binding of the IGF's to matrix, via IGFBP-5, may be important in mediating the cellular growth response to these growth factors.

Effect of Cytokines on Production of Insulin-like Growth Factor Binding Proteins (IGFBPs) from Human Fibroblasts in Culture

“…IGFBP-2, -3, -4 and -6 were detected in the unconcentrated medium after 3 days culture, and we therefore used the conditioned medium collected are 2 days culture in most of the experiments. Previous reports showed that human fibroblasts expressed IGFBP-5 mRNA in human fibroblasts [5], but Western blot failed to detect this species in the present study. This may be due to the preferential binding of IGFBP-5 to extracellular matrix.…”

1α,25‐Dihydroxyvitamin D3 increases IGF binding protein‐5 expression in cultured osteoblasts

“…In contrast to IGFBP-3, IGFBP-5 is preferentially 1:1000, the second (anti-guinea pig, horse-radish peroxidase-conjubound to extracellular matrix in human fibroblast cultures gated, from Anawa, Wangen, Switzerland) at a dilution of 1:500. [11]. Intact IGFBP-5 associates with mouse bone matrix [12].…”

Regulation of Activin A Expression in Mast Cells and Asthma: Its Effect on the Proliferation of Human Airway Smooth Muscle Cells

“…The inflammatory process underlying asthma results from a highly complex interaction of various cell types (3)(4)(5). In addition, ECM interacts with inflammatory cells (6), forms a reservoir for cytokines and growth factors (7,8), influences trafficking of cells (9), and activates granulocytes to increase mediator release and enhance their survival (10,11). Conversely, several inflammatory mediators have a known proliferative effect on airway smooth muscle (ASM) and induce the synthesis of ECM and growth factors in fibroblasts and epithelial cells (12,13).…”