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Kidney Week

Abstract: TH-PO192

Identification and Validation of Neutrophil Extracellular Traps-Associated Genes in Diabetic Kidney Disease: Integration Data from Bulk RNA and Single-Nucleus RNA Sequencing Analyses

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Xie, Ruiyan, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • Tang, Sin Yu Cindy, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • Sher, Ka Ho Jason, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • Zhang, Danting, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • Yap, Yat Hin Desmond, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China

Group or Team Name

  • Dr. Yap, Yat Hin Desmond Team.
Background

Accumulating data shows that immune response has crucial pathogenic contributions in diabetic kidney disease (DKD), but the contribution of Neutrophil Extracellular Traps (NETs) is limited.

Methods

The differentially expressed genes of NETs in human DKD were selected using the bulk RNA-seq of kidney biopsy from DKD patients (GSE30528 and GSE30529). The characteristic NETs-associated genes were further identified by machine learning algorithms. The DKD bulk RNA sequencing (GSE30122) and single-nucleus RNA-seq (GSE195460) were used to validate the genes expression.

Results

Three candidate genes (ITGAM, ITGB2 and TLR7) were all significantly upregulated in human DKD using machine learning approach. Single-cell analysis indicated that the three transcriptional expressions were mostly increased in leucocytes. GSEA further suggested that hub genes play key roles in IL-2/STAT5 signaling pathway (p=0.029). Good diagnostic performance for DKD were also shown. Our polit data validated ITGAM and ITGB2 expressions in the peripheral active neutrophils isolated from DKD patients.

Conclusion

Dysregulation of ITGAM and ITGB2 may play pathogenic roles for DKD, and drugs that target these genes in neutrophil may have therapeutic potential for DKD.

Three identified NETs related genes expression validated in human DKD datasets.

NETs related targets validation in human plasma and DKD neutrophils using RT-qPCR.

Funding

  • Private Foundation Support