胰岛素样生长因子结合蛋白7在急性肾损伤中的作用

The role of insulin-like growth factor binding protein 7 in acute kidney injury

摘要:

急性肾损伤（AKI）是临床常见且高危的综合征，其发病机制复杂，预后差，需早期诊断与干预。胰岛素样生长因子结合蛋白7（IGFBP7）作为应激诱导蛋白，近年来在AKI研究中受到广泛关注。该文系统综述了IGFBP7在AKI中的双重作用：一方面，IGFBP7在肾小管应激早期通过诱导G1期细胞周期阻滞反映损伤信号，与金属蛋白酶抑制因子2（TIMP-2）成为美国食品药品监督管理局批准用于AKI风险预测的关键生物标志物；另一方面，IGFBP7通过调控PARP1、p53、TGF-β/Smad及ERK1/2等信号通路，介导细胞凋亡、衰老及纤维化，参与病程进展。该文总结了IGFBP7在不同临床场景与动物模型中的表达特征与功能机制，指出其在诊断、预后评估及潜在干预中的价值，同时探讨了其病因特异性不足、信号机制不明与转化应用障碍等问题，并展望未来研究方向与精准干预潜力。

Abstract:

Acute kidney injury (AKI) is a common and high-risk clinical syndrome with complex pathogenesis and poor prognosis, requiring early diagnosis and interventions. Insulin-like growth factor binding protein 7 (IGFBP7), as a stress-inducible protein, has received extensive attention in AKI research in recent years. In this paper, we systematically reviewed the dual roles of insulin-like growth factor binding protein 7(IGFBP7) in AKI. On the one hand, it reflects injury signaling by inducing G1-phase cell cycle arrest in the early stage of renal tubular stress; together with tissue inhibitor of metalloproteinases 2 (TIMP-2), it has become a key biomarker approved by the FDA for AKI risk prediction. On the other hand, IGFBP7 participates in disease progression by regulating PARP1, p53, TGF- β/Smad and ERK1/2 signaling pathways, mediating apoptosis, senescence, and fibrosis. This article summarizes the expression characteristics and functional mechanisms of IGFBP7 in different clinical scenarios and animal models, points out its value in diagnosis, prognosis assessment, and potential intervention, explores the challenges of insufficient etiological specificity, unknown signaling mechanisms, and obstacles in translational application, and looks forward to the future research directions and the potential of precision intervention.