Urine proteome analysis in murine nephrotoxic serum nephritis.
BACKGROUND
Urine contains serum proteins filtered by the glomerulus or secreted by the renal tubules and proteins produced locally by the urinary tract. Proteomic analysis of urine holds the potential as a noninvasive means of studying or monitoring disease activity. In mice, large concentrations of albumin and lipocalins have complicated the ability to identify urinary biomarkers in disease models.


METHODS
Passive nephrotoxic serum nephritis was induced in mice. Urine proteins were identified and quantified by iTRAQ and MALDI-TOF mass spectrometry. Results were compared to Western blotting and multiplex immunoassays.


RESULTS
Large concentrations of major urinary proteins dominate the urine proteome of mice even in the context of acute nephritis. Increased proteinuria caused by nephrotoxic serum nephritis is transient and includes increased albumin excretion. There were no alterations in chemokine excretion. Altered hepcidin excretion was identified, most likely reflecting local production and renal retention.


CONCLUSIONS
Proteomic analysis of mouse urine remains challenging due to the abundance of a limited subset of proteins. iTRAQ analysis does not circumvent these challenges, but can provide information on post-translational processing of some proteins. Hepcidin is identified as a potential urinary marker of nephritis and its role in disease pathogenesis warrants further study.
Wenderfer
Scott E
SE
The Brown Foundation Institute of Molecular Medicine, Houston, TX, USA.
Dubinsky
William P
WP
Hernandez-Sanabria
Mayra
M
Braun
Michael C
MC
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000473:pathology / Q000652:urine*; D023181:Antimicrobial Cationic Peptides / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000652:urine*; D064451:Hepcidins; D007118:Immunoassay; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000652:urine; D020543:Proteome; D040901:Proteomics
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C579599:Hamp protein, mouse; C474320:Hamp2 protein, mouse; D064451:Hepcidins; D010455:Peptides; D020543:Proteome