Insulin-like growth factor binding protein 7 (IGFBP7)

Insulin-like growth factor binding protein 7 (IGFBP7) is a secreted glycoprotein that belongs to the IGFBP superfamily, though it is distinguished by its high affinity for insulin and relatively low affinity for IGF-1 and IGF-2 [8, 15]. It serves as a critical regulator of the IGF/insulin signaling axis, modulating cell growth, proliferation, and survival by controlling the bioavailability of these ligands [2, 21]. IGFBP7 is prominently known for its role in inducing G1 cell cycle arrest and cellular senescence, which makes it a vital biomarker for acute kidney injury (AKI) through the FDA-cleared NephroCheck test [1, 4, 13]. In the context of oncology, IGFBP7 acts as a 'double-edged sword,' functioning as a tumor suppressor in some cancers while promoting progression in others, often depending on the tissue microenvironment [2, 11, 17]. Beyond its role as a biomarker, IGFBP7 is being explored as a therapeutic target for heart failure, fibrosis, and cancer, with strategies including neutralizing antibodies and experimental vaccines [9, 11, 13]. However, its context-dependent biological effects and involvement in essential processes like angiogenesis and tissue repair present significant challenges for drug development [11, 13].

Other names

IGFBP-7MAC25IGFBP-rP1AngiomodulinFollistatin-related protein 2PGI2-stimulating factorTumor-derived adhesion factorInsulin-like growth factor-binding protein-related protein 1

IGFBP7 modulates the IGF/insulin signaling axis by binding to insulin with high affinity and to IGF-1/2 with lower affinity, thereby regulating their bioavailability and receptor activation [8, 15, 21]. It induces G1 cell cycle arrest by upregulating cyclin-dependent kinase inhibitors such as p21 and p27 [2, 5]. Additionally, it interacts with the CD93 receptor to regulate angiogenesis and vascular maturation [11]. In heart failure, it promotes cardiac senescence by suppressing FOXO3a through the IGF1R/INSR pathway [13].