Identification and analysis of diverse cell death patterns in diabetic kidney disease using microarray-based...

Area of Science:

• Nephrology
• Molecular Biology
• Genetics

Background:

• Diabetic kidney disease (DKD) is a severe complication of diabetes, characterized by declining renal function.
• Programmed cell death (PCD) pathways are increasingly recognized as critical factors in DKD pathogenesis and potential therapeutic targets.

Purpose of the Study:

• To investigate the role of diverse PCD pathways in DKD.
• To identify core PCDs and develop a predictive risk score for DKD progression.

Main Methods:

• Transcriptome profiling (microarray and snRNA-seq) of DKD samples.
• Analysis of 13 PCD pathways using Gene Set Variation Analysis (GSVA).
• Weighted Gene Co-expression Network Analysis (WGCNA) to identify core genes and construct a Cell Death Signature (CDS) risk score.

Main Results:

• Four core PCD pathways (entotic cell death, apoptosis, necroptosis, pyroptosis) were identified in DKD.
• A CDS risk score based on four genes (CASP1, CYBB, PLA2G4A, CTSS) showed high diagnostic efficiency.
• Higher CDS risk scores correlated with increased immune cell infiltration and reduced glomerular filtration rate (GFR).

Conclusions:

• Multiple PCDs significantly contribute to DKD progression.
• The developed CDS risk score serves as a valuable diagnostic and prognostic tool for DKD.
• These findings highlight potential therapeutic targets for DKD treatment.