Identification of Immune-Related Ferroptosis Biomarkers in Diabetic Kidney Disease and Screening of Associated Inhibitors.

IF 2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Medical Science Pub Date : 2025-07-21 DOI:10.1007/s11596-025-00091-7

Nan-Nan Zhang, Yi Zhu, Qiu-Yan Huang, Fei Hu, Jun Li, Xia Yang

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引用次数: 0

Abstract

Objective: Immune infiltration and ferroptosis play pivotal roles in the progression of diabetic kidney disease (DKD). However, investigations of immune cell-related ferroptosis genes (ICRFGs) in the context of DKD are insufficient. This study aimed to identify ICRFGs relevant to DKD and screen related inhibitors.

Methods: In this study, two DKD datasets from the GEO database were utilized. We adopted the ESTIMATE algorithm to generate microenvironment scores. The CIBERSORT and WGCNA methods were employed to identify immune-related differentially expressed genes (DEGs). The common ICRFGs were derived through a Venn diagram. We employed random forest, LASSO, K-M survival, receiver operating characteristic (ROC) curve, clinical relevance, and Spearman correlation analyses to select hub ICRFGs further. Immunohistochemical experiments were also performed to validate the expression. Additionally, we utilized the Selleck database to obtain ferroptosis-related compounds and used USCF Chimera 1.14 to minimize energy, combined with molecular dynamics (MD) simulations to explore possible ferroptosis inhibitors.

Results: Immunohistochemical analysis revealed that arachidonate 5-lipoxygenase (ALOX5) was significantly highly expressed in the db/db group. Clinical correlation and K-M survival analyses confirmed ALOX5 as the most crucial ICRFG in DKD. Furthermore, ALOX5 was significantly enriched in the terms ECM-receptor interaction, regulation of chemokine production, and regulation of the inflammatory response. A positive correlation was observed between ALOX5 and M1 macrophages, γδ T cells, and monocytes. Moreover, virtual screening and MD revealed NSC348884, salvianolic acid B, and deltarasin as potential ferroptosis inhibitors in combination with ALOX5.

Conclusion: We identified ALOX5 as a reliable and prospective diagnostic marker associated with immunity and ferroptosis in DKD patients.

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糖尿病肾病免疫相关铁下垂生物标志物鉴定及相关抑制剂筛选

目的：免疫浸润和铁下垂在糖尿病肾病（DKD）的进展中起关键作用。然而，在DKD的背景下，对免疫细胞相关铁下垂基因（ICRFGs）的研究还不够。本研究旨在鉴定与DKD相关的icrgs并筛选相关抑制剂。方法：本研究利用GEO数据库中的两个DKD数据集。我们采用ESTIMATE算法生成微环境分数。采用CIBERSORT和WGCNA方法鉴定免疫相关差异表达基因（DEGs）。通过维恩图推导了常见的ICRFGs。我们采用随机森林、LASSO、K-M生存、受试者工作特征（ROC）曲线、临床相关性和Spearman相关分析来进一步选择中心icrgs。免疫组化实验验证表达。此外，我们利用Selleck数据库获得与铁下垂相关的化合物，并使用USCF Chimera 1.14最小化能量，结合分子动力学（MD）模拟探索可能的铁下垂抑制剂。结果：免疫组化分析显示，花生四烯酸5-脂氧合酶（ALOX5）在db/db组显著高表达。临床相关性和K-M生存分析证实ALOX5是DKD中最关键的ICRFG。此外，ALOX5在ecm受体相互作用、趋化因子产生调节和炎症反应调节方面显著富集。ALOX5与M1巨噬细胞、γδ T细胞和单核细胞呈正相关。此外，虚拟筛选和MD显示NSC348884、丹酚酸B和deltarasin与ALOX5联合是潜在的铁下垂抑制剂。结论：我们确定ALOX5是与DKD患者免疫和铁下垂相关的可靠和前瞻性诊断标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.70

自引率

0.00%

发文量

126

期刊介绍： Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.