Dysregulation of neutrophil extracellular traps (NETs)-related genes in the pathogenesis of diabetic kidney disease - Results from bioinformatics analysis and translational studies

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2024-10-11 DOI:10.1016/j.clim.2024.110379

Ruiyan Xie , Ka Ho Jason Sher , Sin Yu Cindy Tang , Irene Ya Lin Yam , C.H. Lee , Qiongli Wu , Desmond Yat Hin Yap

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Abstract

The role of Neutrophil extracellular traps (NETs) in the immunopathogenesis of Diabetic Kidney Disease (DKD) remains elusive. We used a machine learning approach to identify differentially expressed genes (DEGs) associated with NETs in human DKD kidney biopsy datasets and validated the results using single-nucleus RNA sequencing datasets. The expressions of these candidate genes and related cytokines were verified in blood obtained from DKD patients. Three NETs-associated genes (ITGAM, ITGB2 and TLR7) were identified, which all showed significant upregulation in both glomerular and tubulointerstitial compartments in human DKD kidneys. DKD patients showed significantly higher number of activated neutrophils with increased ITGAM and ITGB2 expression, higher serum IL-6 but lower IL-10, compared to healthy controls (p all <0.01). This study suggests that dysregulation of NETs-associated genes ITGAM and ITGB2 are related to the pathogenesis of DKD, and may serve as novel diagnostic markers and therapeutic targets in DKD.

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中性粒细胞胞外捕获物（NET）相关基因在糖尿病肾病发病机制中的失调--生物信息学分析和转化研究的结果

中性粒细胞胞外捕获物（NET）在糖尿病肾病（DKD）免疫发病机制中的作用仍然难以捉摸。我们使用机器学习方法在人类 DKD 肾活检数据集中识别了与 NET 相关的差异表达基因（DEGs），并使用单核 RNA 测序数据集验证了结果。这些候选基因和相关细胞因子的表达在 DKD 患者的血液中得到了验证。结果发现了三个与NET相关的基因（ITGAM、ITGB2和TLR7），这些基因在人类DKD肾脏的肾小球和肾小管间质中都出现了显著的上调。与健康对照组相比，DKD 患者的活化中性粒细胞数量明显增多，ITGAM 和 ITGB2 表达增加，血清 IL-6 增高，但 IL-10 降低（P 均为 <0.01）。这项研究表明，NET相关基因ITGAM和ITGB2的失调与DKD的发病机制有关，可作为DKD的新型诊断标志物和治疗靶点。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.