The Glomerulus Multiomics Analysis Provides Deeper Insights into Diabetic Nephropathy

Abstract

Although diabetic nephropathy (DN) is the leading cause of the end-stage renal disease, the exact regulation mechanisms remain unknown. In this study, we integrated the transcriptomics and proteomics profiles of glomeruli isolated from 50 biopsy-proven DN patients and 25 controls to investigate the latest findings about DN pathogenesis. First, 1152 genes exhibited differential expression at the mRNA or protein level, and 364 showed significant association. These strong correlated genes were divided into four different functional modules. Moreover, a regulatory network of the transcription factors (TFs)−target genes (TGs) was constructed, with 30 TFs upregulated at the protein levels and 265 downstream TGs differentially expressed at the mRNA levels. These TFs are the integration centers of several signal transduction pathways and have tremendous therapeutic potential for regulating the aberrant production of TGs and the pathological process of DN. Furthermore, 29 new DNspecific splice-junction peptides were discovered with high confidence; these peptides may play novel functions in the pathological course of DN. So, our in-depth integrative transcriptomicsproteomics analysis provided deeper insights into the pathogenesis of DN and opened the potential avenue for finding new therapeutic interventions. MS raw files were deposited into the proteomeXchange with the dataset identifier PXD040617.