糖尿病肾病铁下垂相关基因的鉴定和验证
Identification and validation of ferroptosis-related genes for diabetic nephropathy.
摘要(中文译文)
新出现的证据强调了铁死亡在糖尿病肾病(DN)病理生理学中的关键作用。本研究旨在通过生物信息学分析和实验验证，识别糖尿病肾病中潜在的铁死亡相关基因(FRGs)。糖尿病肾病数据集和铁死亡相关基因集分别从基因表达综合数据库(GEO)和铁死亡数据库中获取。通过差异表达分析识别糖尿病肾病中的铁死亡相关差异表达基因(DE-FRGs)，并应用机器学习筛选关键基因。利用受试者工作特征(ROC)曲线分析评估风险模型的准确性。同时探索了与DE-FRGs及糖尿病肾病相关的潜在小分子化合物。通过定量逆转录PCR(qRT-PCR)检测糖尿病肾病小鼠肾脏中DE-FRGs的表达，并通过酶联免疫吸附试验(ELISA)检测糖尿病肾病患者与非糖尿病肾病对照组血清中的表达。分析共识别出125个DE-FRGs，富集于铁死亡及糖尿病肾病相关通路。机器学习筛选出9个诊断生物标志物，并通过ROC曲线进行验证，同时发现13种潜在治疗化合物。在DE-FRGs中，qRT-PCR验证了糖尿病肾病肾脏中白细胞介素-33(IL-33)、视黄酸受体应答蛋白2(RARRES2)、zeste同源增强子2(EZH2)、间隙连接蛋白α1(GJA1)和缺氧诱导脂滴相关蛋白(HILPDA)的表达失调。重要的是，糖尿病肾病患者血清中EZH2和IL-33水平显著升高，凸显了它们在发病机制中的关键作用及作为治疗靶点的潜力。总之，本研究确定了IL-33和EZH2为糖尿病肾病中的关键DE-FRGs，为该疾病的分子机制提供了新的见解。
Abstract
Emerging evidence highlights the pivotal role of ferroptosis in the pathophysiology of diabetic nephropathy (DN). This study aimed to identify potential ferroptosis-related genes (FRGs) in DN through bioinformatics and experimental validation. Datasets for diabetic nephropathy (DN) and ferroptosis-related gene sets were obtained from the Gene Expression Omnibus (GEO) database and the Ferroptosis Database, respectively. Differential expression analysis identified ferroptosis-related genes (DE-FRGs) in DN, and machine learning was applied to screen key genes. The risk model's accuracy was evaluated using receiver operating characteristic (ROC) curve analysis. Potential small chemical compounds associated with DE-FRGs and DN were also explored. Expression of DE-FRGs was measured by Quantitative Reverse Transcription PCR (qRT-PCR) in kidneys of DN mice and by Enzyme-linked immunosorbent assay (ELISA) in serum from DN patients versus non-DN controls. Analysis identified 125 DE-FRGs enriched in ferroptosis and DN-related pathways. Machine learning pinpointed nine diagnostic biomarkers, which were validated by ROC curves, and 13 potential therapeutic compounds. Among the DE-FRGs, qRT-PCR verified dysregulation of interleukin-33 (IL-33), retinoic acid receptor responder protein 2 (RARRES2), enhancer of zeste homolog 2 (EZH2), gap junction protein alpha 1 (GJA1), and hypoxia-inducible lipid droplet associated (HILPDA) in DN kidneys. Importantly, serum levels of EZH2 and IL-33 were significantly elevated in DN patients, underscoring their critical role in pathogenesis and potential as therapeutic targets. In conclusion, this study identified IL-33 and EZH2 as key DE-FRGs in DN, offering new insights into the molecular mechanisms underlying the disease.
如何引用
AMA
Hao Duan, Yanqiu Wang, Qiao Wang, Jie Yan, Xingyu Fan, Wenyan Wu, et al. Identification and validation of ferroptosis-related genes for diabetic nephropathy.. European journal of pharmacology. 2026; doi:10.1016/j.ejphar.2026.178779.
APA
Hao Duan, Yanqiu Wang, Qiao Wang, Jie Yan, Xingyu Fan, Wenyan Wu, et al (2026). Identification and validation of ferroptosis-related genes for diabetic nephropathy.. European journal of pharmacology. https://doi.org/10.1016/j.ejphar.2026.178779
GB/T 7714
Hao Duan, Yanqiu Wang, Qiao Wang, Jie Yan, Xingyu Fan, Wenyan Wu, et al. Identification and validation of ferroptosis-related genes for diabetic nephropathy.[J]. European journal of pharmacology, 2026 doi:10.1016/j.ejphar.2026.178779.
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