Regulation of Insulin-Like Growth Factor-I (IGF-I) Delivery by IGF Binding Proteins and Receptors

ArticleinAnnals of Biomedical Engineering 34(4):618-32 · May 2006with16 Reads
DOI: 10.1007/s10439-005-9064-6 · Source: PubMed
Abstract
Delivery of growth factors via the bloodstream for the treatment of various diseases is regulated in part by interactions with cell surface binding elements. Understanding the kinetics of growth factor binding and transport by cells would, therefore, be advantageous. This report quantifies the binding, internalization, and transport of insulin-like growth factor-I (IGF-I) across bovine aortic endothelial cells (BAEC) cultured in vitro. Binding analysis indicated that IGF binding proteins (IGFBPs), primarily localized with the extracellular matrix, were the primary IGF-I binding elements in our system, with twice as many binding sites (8.0 +/- 1.9 x 10(4) per cell) as IGF-I receptors (IGF-IR) (3.9 +/- 0.6 x 10(4) per cell). Internalization of IGF-I by IGF-IR, but not IGFBPs, was detected, however both receptor and IGFBP binding were shown to inhibit rather than enhance the transport of intact IGF-I, albeit in different ways. IGFBPs retained IGF-I in the apical region while IGF-IR binding led to protein degradation. Based on our computational modeling and experimental data, we hypothesize that IGFBPs could function as a reservoir for IGF-I, sequestering it for later release and transport, and that this reservoir function of the IGFBPs could be used to promote controlled localized delivery of IGF-I.
    • "When trafficking in the ECM of IVD, IGF-1 competitively reacts with IGFBP and IGF-1R [82]. By interacting with the binding protein, a bound complex (IGF-1/IGFBP) forms. "
    Full-text · Dataset · Sep 2015 · PLoS Computational Biology
    • "When trafficking in the ECM of IVD, IGF-1 competitively reacts with IGFBP and IGF-1R [82]. By interacting with the binding protein, a bound complex (IGF-1/IGFBP) forms. "
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    • "Once IGFI is bound to IGFBP2, IGFI becomes inactive and cannot bind to IGFIR or activate downstream signaling. IGFBP2 acts as reservoir for IGFI as it sequesters IGFI for release at a later time [64]. An increase in IGFI concentration leads to the activation of HIF1α through the RAS pathway [61]; and furthermore, it leads to increased production of HIF1α [61] . "
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