Bioinformatics Analysis Reveals a Shared Pathway for Common Forms of Adult Nephrotic Syndrome.

Abstract

Focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and minimal change disease (MCD) are common causes of nephrotic syndrome. Although triggers for these diseases differs, disease progression may share common molecular mechanisms. The aim of this study was to investigate the presence of molecular pathways that are dysregulated across these glomerular diseases. The gene expression dataset GSE200828 from the NEPTUNE Study was obtained from the GEO database. R and Python packages, Cytoscape software, and online tools (DAVID and STRING) were used to identify core genes and topologically relevant nodes and molecular pathways. Single cell RNA sequencing analysis was applied to identify expression patterns of core genes across kidney cell types in glomerular compartments. A total of 1087 differentially expressed genes (DEGs) were identified, including 691 up-regulated genes and 396 down-regulated genes, common in all three forms of nephrotic syndrome compared to kidney donor controls (FDR p<0.01). A multi-approach bioinformatics analysis narrowed down 28 genes similarly dysregulated across the three proteinuric glomerulopathies. The most topologically relevant nodes belonged to the adherens junction, focal adhesion, and cytoskeleton pathways, where zyxin covers all of those Gene Ontology terms. We report that dysregulation of cell adhesion complexes was present in the three most common forms of glomerular disease. Zyxin could be a biomarker in all three common forms of nephrotic syndrome. If further functional studies confirm its role in their development, zyxin could be a potential therapeutic target.