Abstract:
Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) is an extracellular matrix (ECM) glycoprotein, highly enriched in activated vasculature during development, physiological and pathological tissue remodeling. Despite decades of research, its role in tissue (re-)vascularization is highly ambiguous, exhibiting pro- and anti-angiogenic properties in different tissue remodeling states. IGFBP7 has multiple binding partners, including structural ECM components, cytokines, chemokines, as well as several receptors. Based on current evidence, it is suggested that IGFBP7\'s bioactivity is strongly dependent on the microenvironment it is embedded in. Current studies indicate that during physiological angiogenesis, IGFBP7 promotes endothelial cell attachment, luminogenesis, vessel stabilization and maturation. Its effects on other stages of angiogenesis and vessel function remain to be determined. IGFBP7 also modulates the pro-angiogenic properties of other signaling factors, such as VEGF-A and IGF, and potentially acts as a growth factor reservoir, while its actual effects on the factors\' signaling may depend on the environment IGFBP7 is embedded in. Besides (re-)vascularization, IGFBP7 clearly promotes progenitor and stem cell commitment and may exhibit anti-inflammatory and anti-fibrotic properties. Nonetheless, its role in inflammation, immunomodulation, fibrosis and cellular senescence is again likely to be context-dependent. Future studies are required to shed more light on the intricate functioning of IGFBP7.
摘要:
胰岛素样生长因子结合蛋白7(IGFBP7)是一种细胞外基质(ECM)糖蛋白,在发育过程中高度富含活化的脉管系统,生理和病理组织重塑。尽管经过几十年的研究,它在组织(再)血管化中的作用是高度模糊的,在不同的组织重塑状态下表现出促血管生成和抗血管生成特性。IGFBP7有多个结合伴侣,包括结构ECM部件,细胞因子,趋化因子,以及几个受体。根据目前的证据,这表明IGFBP7的生物活性强烈依赖于它嵌入的微环境。目前的研究表明,在生理性血管生成过程中,IGFBP7促进内皮细胞附着,发光,血管稳定和成熟。其对血管生成和血管功能的其他阶段的影响仍有待确定。IGFBP7还调节其他信号因子的促血管生成特性,如VEGF-A和IGF,并可能充当生长因子的蓄水池,而其对信号传导因素的实际影响可能取决于IGFBP7嵌入的环境。除了(再)血管化,IGFBP7明显促进祖细胞和干细胞的定型,并可能表现出抗炎和抗纤维化特性。尽管如此,它在炎症中的作用,免疫调节,纤维化和细胞衰老再次可能是环境依赖性的。未来的研究需要进一步阐明IGFBP7的复杂功能。