Qian Hengrong, Gao Sheng, Zhang Ting, Xie Yuanyuan, Chen Siyan, Hong Yanggang, Wu Xinlei, Xing Zhouhang, Kong Lingjie, Mo Jintao, Lin Yiming, Zheng Anzhe, Wang Wenqian, Wang Liangxing, Hua Chunyan
School of the 2nd Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.
Laboratory Animal Center, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.
J Inflamm Res. 2025 Mar 14;18:3859-3878. doi: 10.2147/JIR.S500115. eCollection 2025.
Systemic lupus erythematosus (SLE) is characterized by aberrant immune activation and disrupted iron metabolism, yet the molecular mediators that govern both processes remain unclear. This study aims to identify pivotal genes that modulate immune responses and iron metabolism, and to delineate their contributions to SLE pathogenesis.
Differentially expressed genes related to iron metabolism (IM-DEGs) were identified using datasets (GSE72326, GSE110169, GSE126307, and GSE50772) from the GEO database and the MSigDB. Functional enrichment analyses were performed on the iron metabolism related genes (IM-Genes). A weighted gene co-expression network analysis was constructed to identify hub genes, which were further refined as potential biomarkers using the least absolute shrinkage and selection operator method. The predictive value of these biomarkers was validated using receiver operating characteristic (ROC) curves and the nomogram. CIBERSORT was employed to evaluate immune cell infiltration in SLE. Additionally, the expression and function of were confirmed using RNA interference, quantitative real-time PCR, and Western blotting techniques.
Bioinformatics analyses identified 4 potential biomarkers: , and exhibited the highest clinical validity (AUC = 0.927) and was closely associated with classic diagnostic indicators. Its diagnostic potential was confirmed through ROC curve and nomogram, highlighting its role in SLE pathogenesis. Elevated expression was observed in peripheral blood mononuclear cells of SLE patients, positively correlating with activated dendritic cells (DCs). Notably, knockdown markedly impaired the function of activated DCs, as evidenced by suppressed expression of inflammatory mediators and iron metabolism-related genes.
Our findings suggest that is a potential diagnostic biomarker and therapeutic target for SLE, elucidating the intricate relationship between immune dysregulation and aberrant iron metabolism in activated DCs, which exacerbates SLE.
系统性红斑狼疮（SLE）的特征是异常的免疫激活和铁代谢紊乱，但调控这两个过程的分子介质仍不清楚。本研究旨在识别调节免疫反应和铁代谢的关键基因，并阐明它们在SLE发病机制中的作用。
使用来自基因表达综合数据库（GEO数据库）和分子特征数据库（MSigDB）的数据集（GSE72326、GSE110169、GSE126307和GSE50772）识别与铁代谢相关的差异表达基因（IM-DEGs）。对铁代谢相关基因（IM-基因）进行功能富集分析。构建加权基因共表达网络分析以识别枢纽基因，并使用最小绝对收缩和选择算子方法将其进一步优化为潜在生物标志物。使用受试者工作特征（ROC）曲线和列线图验证这些生物标志物的预测价值。采用CIBERSORT评估SLE中的免疫细胞浸润。此外，使用RNA干扰、定量实时PCR和蛋白质印迹技术确认了[此处原文缺失具体基因名称]的表达和功能。
生物信息学分析确定了4个潜在生物标志物：[此处原文缺失具体基因名称]，[此处原文缺失具体基因名称]表现出最高的临床有效性（AUC = 0.927），并与经典诊断指标密切相关。通过ROC曲线和列线图证实了其诊断潜力，突出了其在SLE发病机制中的作用。在SLE患者的外周血单个核细胞中观察到[此处原文缺失具体基因名称]表达升高，与活化的树突状细胞（DCs）呈正相关。值得注意的是，[此处原文缺失具体基因名称]敲低显著损害了活化DCs的功能，炎症介质和铁代谢相关基因的表达受到抑制证明了这一点。
我们的研究结果表明，[此处原文缺失具体基因名称]是SLE的潜在诊断生物标志物和治疗靶点，阐明了活化DCs中免疫失调与异常铁代谢之间的复杂关系，这加剧了SLE。
