Abstract:

ABSTRACT Objective: To profile comprehensively urine proteomics and screen differentially expressed urine protein in membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) patients with nephrotic syndrome. Methodology: Fifteen MN patients and fifteen FSGS patients with nephrotic syndrome were enrolled into this study. Their urine samples were analyzed by Albumin/IgG antibody depletion combined with iTRAQ (isobaric tags for relative and absolute quantitation) labeled 2D-LC MS/MS(Two dimensional liquid chromatography-tandem mass spectrometry) for profiling urine proteomics and screening differentially expressed urine proteins. GO（Gene ontology）analysis was used to categorize identified protein and differentially expressed proteins according to molecular function、biological process and cellular component. The top 10 proteins in identified protein were compared with the top 10 proteins in plasma proteomics. Results: A total of 809 urine proteins were identified in MN and FSGS patients with nephrotic syndrome, of which 16 were differentially expressed between the two groups of subjects. GO analysis revealed that the molecular function of identified protein mainly included catalytic activity、binding and receptor activity, the biological process mainly involved metabolic process、cellular process and development process, the cellular component mainly contained extracellular region、cell part and extracellular matrix. The biological process of differentially expressed proteins involved fibrinolysis regulation、immune reaction、metabolic process、cell proliferation and so on. The top 10 proteins in urine proteomics from patients with nephrotic syndrome of MN and FSGS were compared with the top 10 proteins in plasma proteomics, which suggested even in pathological condition, the kidney may keep handling function for different protein, and proteinuria proteomics may has a different arctecture with plasma proteomics. Conclusion: Our proteinuria proteomics profile was the largest for now and provided a basis for future study. Our differentially expressed protein need to be validated as biomarkers for diagnosis, therapy and prognosis.

Key words: proteomics, MN,  FSGS, iTRAQ, biomarker