381-P: Identification and Functional Analysis of ZFP36, the Hub Ferroptosis-Related Factor in Diabetic Kidney Disease

Introduction and Objective: Diabetic Kidney Disease (DKD) is a leading cause of end-stage renal disease (ESRD). Extensive studies suggest that ferroptosis is a key factor in DKD progression. Our research aims to investigate whether ferroptosis-related factor ZFP36 can alleviate diabetic kidney injury. Methods: We extracted differentially expressed genes from the GEO database and conducted GO enrichment, GSEA, GSVA, plus machine learning techniques like RF, SVM-RFE, and Lasso Cox regression to identify ferroptosis-related genes. Expression differences of ZFP36 and its interacting proteins were validated in HK-2 cells and DKD mouse models. Additionally, ZFP36's interaction with traditional Chinese herbal components was assessed using AutoDock Tools to evaluate their impact on DKD ferroptosis. Results: We identified 9 genes significantly associated with both ferroptosis and DKD. Further machine learning marked ZFP36 as a central gene. In vivo experiments showed that compared to the control group, the expression of ZFP36 is reduced in the DKD model group. In vitro, overexpression of ZFP36 alleviates high-glucose-induced ferroptosis and reduce the formation of extracellular matrix components such as FN1 and α-SMA.ZFP36 interacts with Nrf2, reducing ROS and MDA levels, and increasing GSH levels, indicates that ZFP36 can alleviate oxidative stress. Molecular docking analysis shows that traditional Chinese herbs like Berberine and Jatrorrhizine positively regulating ferroptosis in DKD, exhibit high affinity for ZFP36, suggesting it mediates their renal protective effect. Conclusion: This study illuminates the emerging role of ZFP36 in ferroptosis in DKD, emphasizing its potential as a therapeutic target. This provides new insights for the development of targeted therapies for DKD. Disclosure A. Li: None. M. Shi: None. W. Gu: None. Y. Chen: None. Y. Liu: None. J. Zhang: None. Y. Yuxuan: None. C. Huimin: None. J. Chen: None. H. Zhang: None. Funding Huai'an Science and Technology Bureau (BE2023745), Jiangsu Provincial Health Commission (H2023137)