The Glomerulus Multiomics Analysis Provides Deeper Insights into Diabetic Nephropathy

Although diabetic nephropathy (DN) is the leading causeof theend-stage renal disease, the exact regulation mechanisms remain unknown.In this study, we integrated the transcriptomics and proteomics profilesof glomeruli isolated from 50 biopsy-proven DN patients and 25 controlsto investigate the latest findings about DN pathogenesis. First, 1152genes exhibited differential expression at the mRNA or protein level,and 364 showed significant association. These strong correlated geneswere divided into four different functional modules. Moreover, a regulatorynetwork of the transcription factors (TFs)-target genes (TGs)was constructed, with 30 TFs upregulated at the protein levels and265 downstream TGs differentially expressed at the mRNA levels. TheseTFs are the integration centers of several signal transduction pathwaysand have tremendous therapeutic potential for regulating the aberrantproduction of TGs and the pathological process of DN. Furthermore,29 new DN-specific splice-junction peptides were discovered with highconfidence; these peptides may play novel functions in the pathologicalcourse of DN. So, our in-depth integrative transcriptomics-proteomicsanalysis provided deeper insights into the pathogenesis of DN andopened the potential avenue for finding new therapeutic interventions.MS raw files were deposited into the proteomeXchange with the datasetidentifier PXD040617.