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The role and regulation of IGFBP-1 phosphorylation in fetal growth restriction

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Fetal growth restriction (FGR) increases the risk of perinatal complications and predisposes the infant to developing metabolic, cardiovascular, and neurological diseases in childhood and adulthood. The pathophysiology underlying FGR remains poorly understood and there is no specific treatment available. Biomarkers for early detection are also lacking. The insulin-like growth factor (IGF) system is an important regulator of fetal growth. IGF-I is the primary regulator of fetal growth, and fetal circulating levels of IGF-I are decreased in FGR. IGF-I activity is influenced by a family of IGF binding proteins (IGFBPs), which bind to IGF-I and decrease its bioavailability. During fetal development the predominant IGF-I binding protein in fetal circulation is IGFBP-1, which is primarily secreted by the fetal liver. IGFBP-1 binds IGF-I and thereby inhibits its bioactivity. Fetal circulating levels of IGF-I are decreased and concentrations of IGFBP-1 are increased in FGR. Phosphorylation of human IGFBP-1 at specific sites markedly increases its binding affinity for IGF-I, further limiting IGF-I bioactivity. Recent experimental evidence suggests that IGFBP-1 phosphorylation is markedly increased in the circulation of FGR fetuses suggesting an important role of IGFBP-1 phosphorylation in the regulation of fetal growth. Understanding of the significance of site-specific IGFBP-1 phosphorylation and how it is regulated to contribute to fetal growth will be an important step in designing strategies for preventing, managing, and/or treating FGR. Furthermore, IGFBP-1 hyperphosphorylation at unique sites may serve as a valuable biomarker for FGR.

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Acknowledgments

This work was supported by grants from the National Institute of Health (HD078313 and HD071306), the Lawson and the Children’s Health Research Institutes.

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  1. Departments of Pediatrics and Biochemistry, Children’s Health Research Institute, University of Western Ontario, VRL Room A5-136 (WC) 800 Commissioners Road E., London, ON, N6C 2V5, Canada

    Madhulika B. Gupta

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Correspondence to Madhulika B. Gupta.

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Gupta, M.B. The role and regulation of IGFBP-1 phosphorylation in fetal growth restriction. J. Cell Commun. Signal. 9, 111–123 (2015). https://doi.org/10.1007/s12079-015-0266-x

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