Pursuing Diabetic Nephropathy through Aqueous Humor Proteomics Analysis

In order to determine the possible aqueous humor (AH) proteins involved in diabetic nephropathy (DN) progression, we performed gel electrophoresis-liquid chromatography-tandem mass spectrometry protein profiling of AH samples from 5 patients with proliferative diabetic retinopathy (PDR) combined DN and 5 patients with PDR. Function enrichment analyses were carried out after the identification of differentially expressed proteins (DEPs). Protein-protein interaction networks were then built and the Search Tool for the Retrieval of Interacting Genes database and CytoNCA plugin in Cytoscape were utilized for module analysis. Ingenuity Pathway Analysis (IPA) was used to analyze disease and biological function, Tox function enrichment and upstream regulatory molecules/networks. Fifty-four DEPs were finally confirmed, whose enriched functions and pathways covered cell adhesion, extracellular exosome, complement activation, complement and coagulation cascades, etc. Nine hub genes were identified, including NCAM1, PLG, APOH, C3, PSAP, RBP4, CDH2, NUCB1, and GNS. IPA showed that C3 and PLG are involved in renal and urological system abnormalities. Conclusively, DEPs and hub proteins confirmed in this exploratory AH proteomic analysis may help us gain a deeper understanding of the molecular mechanisms involved in DN progression, providing novel candidate biomarkers for the early detection for diagnosis of DN.