The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases
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REVIEW
The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases Fei Song . Xiao-Xia Zhou . Yu Hu . Gang Li
. Yan Wang
Received: September 10, 2020 / Accepted: November 19, 2020 Ó Springer Healthcare Ltd., part of Springer Nature 2020
ABSTRACT The insulin-like growth factor (IGF) system comprises ligands of IGF-I/II, IGF receptors (IGFR), IGF binding proteins (IGFBPs), and IGFBP hydrolases. The IGF system plays multiple roles during various disease development as IGFs are widely involved in cell proliferation and differentiation through regulating DNA transcription. Meanwhile, IGFBPs, which are mainly synthesized in the liver, can bind to IGFs and perform two different functions: either inhibition of IGFs by forming inactive compounds with IGF or enhancement of the function of IGFs by strengthening the IGF–IGFR interaction. Interestingly, IGFBPs may have wider functions through IGF-independent mechanisms. Studies have shown that IGFBPs play important roles in cardiovascular disease, tumor progression, fetal growth, and neuronutrition. In this review, we emphasize that different IGFBP family members have common or unique functions in numerous diseases; moreover, IGFBPs may serve as biomarkers for disease diagnosis and prediction.
F. Song X.-X. Zhou Y. Hu G. Li (&) Y. Wang (&) Xiamen Cardiovascular Hospital, Xiamen University, Xiamen 361015, Fujian, China e-mail: [email protected]. Wang e-mail: [email protected]
Keywords: Disease development; Insulin-like growth factor binding proteins; Insulin-like growth factors Key Summary Points IGFBPs are mainly synthesized in the liver and can bind to IGFs and perform two different functions, inhibiting the IGFs or strengthening the interaction between IGFs and IGF receptors. IGFBP family members have the same or different functions in numerous diseases. IGFBPs may be used as biomarkers for disease diagnosis and prediction.
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Adv Ther
INTRODUCTION Insulin-like growth factor (IGF) signaling is essential for growth and cell survival as it suppresses apoptosis and promotes cell cycle progression, angiogenesis, and metastatic activities [1–4]. The activation of the IGF system is dependent on ligands of IGF-I/II, IGF receptor (IGFR), IGFR binding protein (IGFBP), and IGFBP hydrolase [5, 6]. IGF-I and IGF-II are short amino acids peptides that are secreted by multiple cell types [4, 7] and function as endocrine hormones [8]. The activation of IGF signaling is mediated through IGF–IGFR binding, and IGFBPs could also participate to affect the function of IGFs [5, 7, 9]. IGFBPs are binding proteins of IGFs and regulate the turnover, transport, or tissue distribution of IGFs [10]. Owing to the important roles of IGF in growth regulation, research on the IG
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