Indoxyl Sulfate-Mediated Metabolic Alteration of Transcriptome Signatures in Monocytes of Patients with End-Stage Renal Disease (ESRD)

Abstract

End-stage renal disease (ESRD) is the final stage of chronic kidney disease, which is increasingly prevalent worldwide and is associated with the progression of cardiovascular disease (CVD). Indoxyl sulfate (IS), a major uremic toxin, plays a key role in the pathology of CVD via adverse effects in endothelial and immune cells. Thus, there is a need for a transcriptomic overview of IS responsive genes in immune cells of ESRD patients. Here, we investigated IS-mediated alterations in gene expression in monocytes from ESRD patients. Transcriptomic analysis of ESRD patient-derived monocytes and IS-stimulated monocytes from healthy controls was performed, followed by analysis of differentially expressed genes (DEGs) and gene ontology (GO). We found that 148 upregulated and 139 downregulated genes were shared between ESRD patient-derived and IS-stimulated monocytes. Interaction network analysis using STRING and ClueGo suggests that mainly metabolic pathways, such as the pentose phosphate pathway, are modified by IS in ESRD patient-derived monocytes. These findings were confirmed in IS-stimulated monocytes by the increased mRNA expression of genes including G6PD, PGD, and TALDO1. Our data suggest that IS causes alteration of metabolic pathways in monocytes of ESRD patients and, thus, these altered genes may be therapeutic targets.