IGF2BP2在干性年龄相关性黄斑变性发病机制中巨噬细胞介导的NLRP3炎性小体激活中的作用。

The role of IGF2BP2 in macrophage-mediated NLRP3 inflammasome activation in the pathogenesis of dry AMD.

作者信息

Zhao Yuqing, Zhang Yu, Li Junfang, Zhang Yifei, Qu Yi

机构信息

Department of Geriatrics, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, China.

Key Laboratory of Cardiovascular Proteomics of Shandong Province, Jinan, China.

出版信息

Biol Direct. 2025 Apr 22;20(1):57. doi: 10.1186/s13062-025-00648-5.

DOI:10.1186/s13062-025-00648-5

PMID:40264207

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12016075/

Abstract

BACKGROUND

Dry age-related macular degeneration (AMD) is a common chronic degenerative eye disease for which there is currently no effective treatment. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a recently identified m6A reader that binds RNA and maintains its stability, thereby participating in various biological processes. However, its role in dry AMD remains unclear.

METHODS

In this study, we investigated the role of IGF2BP2 in macrophage NLRP3 inflammasomes using a sodium iodate-induced dry AMD model.

RESULTS

Our results demonstrated that IGF2BP2 is highly expressed in the retinal-choroidal tissue induced by sodium iodate, with its effects primarily occurring in macrophages. The loss of IGF2BP2 ameliorating dry AMD. Mechanistically, methylated NLRP3 transcripts were subsequently directly recognized by the specific m 6 A "reader", IGF2BP2, to prevent NLRP3 mRNA degradation. Furthermore, in in vivo experiments, to maintain the eye's "immune privilege", we employed mesoporous silica-based cell therapy to target and regulate macrophage IGF2BP2, providing a foundation for the evaluation and translation of therapies targeting this gene.

CONCLUSION

our study reveals that the molecular mechanism of dry AMD pathogenesis involves IGF2BP2-mediated NLRP3 inflammasome activation in macrophages, highlighting IGF2BP2 as a promising biomarker and therapeutic target for dry AMD treatment.

摘要

背景

干性年龄相关性黄斑变性（AMD）是一种常见的慢性退行性眼病，目前尚无有效的治疗方法。胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）是最近发现的一种m6A阅读器，它与RNA结合并维持其稳定性，从而参与各种生物学过程。然而，其在干性AMD中的作用仍不清楚。

方法

在本研究中，我们使用碘酸钠诱导的干性AMD模型研究了IGF2BP2在巨噬细胞NLRP3炎性小体中的作用。

结果

我们的结果表明，IGF2BP2在碘酸钠诱导的视网膜脉络膜组织中高表达，其作用主要发生在巨噬细胞中。IGF2BP2的缺失改善了干性AMD。从机制上讲，甲基化的NLRP3转录本随后被特异性m6A“阅读器”IGF2BP2直接识别，以防止NLRP3 mRNA降解。此外，在体内实验中，为了维持眼睛的“免疫特权”，我们采用基于介孔二氧化硅的细胞疗法来靶向和调节巨噬细胞IGF2BP2，为评估和转化针对该基因的疗法提供了基础。