类胰岛素生长因子结合蛋白IGFBP-3的研究进展

Research Progress of Insulin-Like Growth Factor Binding Protein IGFBP-3

类胰岛素生长因子(Insulin-like growth factor,IGF)信号系统是进化上非常保守的信号转导途径,包括2个IGF配体、2个IGF受体和6个IGF结合蛋白(IGF binging protein,IGFBP)。IGFBP能结合IGF并调节其作用。IGFBP-3是血液中主要的IGF载体蛋白。离体(in vitro)实验研究发现,IGFBP-3可以抑制或促进IGF的作用,在缺乏IGF受体的细胞中IGFBP-3仍然具有活性。由此可见,IGFBP-3除了具有IGF依赖性作用,还具有IGF非依赖性作用。此外还发现IG-FBP-3能定位于细胞核并与类视黄醇X受体-α(Retinoid X receptor-α,RXRα)结合。越来越多的研究结果显示出IGFBP-3在生物体内作用的复杂性,使探讨IGFBP-3体内(in vivo)作用机制的研究成为热点。本文综述了IGFBP-3的功能、作用机制,与肿瘤、血管生成的关系,以及正常状态下IGFBP-3的生理功能。

The insulin-like growth [actor （IGF） system is an evolutionarily conserved signaling pathway that is composed of two IGF ligands, two IGF receptors, and six IGF binging proteins （IGFBPs）. The IGFBPs bind IGF and modulate IGF activities. IGFBP-3 is the major IGF carrier protein in the bloodstream. In vitro, IGFBP-3 can inhibit or potentiate IGF actions and even possesses the activities in IGF receptor null cells, suggesting that IGFBP-3 have both IGF-dependent and independent actions. In addition, IGFBP-3 is localized in the nucleus and can interact with retinoid X receptor-α. The functions of IG- FBP-3 in vivo, however, are not clear. In this article, we summarize the function, mechanistic basis, relations with tumor, angiogenesis, as well as physiological function of IGFBP-3.