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

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2024-11, Vol.268, p.110379, Article 110379
• Main Authors: Xie, Ruiyan, Sher, Ka Ho Jason, Tang, Sin Yu Cindy, Yam, Irene Ya Lin, Lee, C.H., Wu, Qiongli, Yap, Desmond Yat Hin
• Format: Article
• Language: English
• Subjects: CD11b Antigen - genetics; Computational Biology - methods; Diabetic kidney disease; Diabetic Nephropathies - genetics; Diabetic Nephropathies - immunology; Extracellular Traps - genetics; Extracellular Traps - immunology; Female; Humans; Interleukin-6 - genetics; ITGAM; ITGB2; Kidney - pathology; Machine Learning; Male; Middle Aged; Neutrophil extracellular trap; Neutrophils - immunology; Translational Research, Biomedical
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110379

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