Identification of Ribonuclease 6 as an immunoinflammatory key gene associated with the glomerular injury in diabetic nephropathy

Abstract

Diabetic nephropathy is one of the major causes of end-stage renal disease, and the pathogenesis of the disease has not been elucidated. While the immunoinflammatory response plays an essential role in the progression of diabetic nephropathy. Glomerular expression dataset in diabetic nephropathy was obtained from the GEO database. Differentially expressed genes were identified and functional enrichment analysis was performed to find genes associated with immunity and inflammation from them. The hub genes of immunoinflammatory were identified using MCODE after establishing the PPI network and gene expression was verified with diabetic nephropathy model rats. Xcell was used to assign immune cells to diabetic nephropathy glomerular samples to detect significant changes in immune cells and to analyze correlations with the hub gene. We found 120 DEGs associated with immunity and inflammation, Ribonuclease 6 was the Hub gene with the highest MCODE score. Xcell analysis revealed significant changes of immune cells in DN glomeruli, including upregulated Activated DCs, Conventional DCs, CD4+ Tem, Epithelial cells, Macrophages, Macrophages M1, and Memory B-cells. RNase6 expression showed the highest positive correlation with Macrophages M1, Activated DCs, and Conventional DCs. We verified through the Nephroseq v5 database that RNase6 expression was elevated in DN glomeruli and negatively correlated with glomerular filtration rate. Animal studies revealed that the kidney of DN model rats showed increased RNase6 expression together with inflammatory factor TNF-alpha and chemokine MCP-1. Our study identified RNase6 as a diagnostic and prognostic biomarker for diabetic nephropathy and found that it may play an essential role in the immunoinflammatory damage to the glomerulus.