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Int J Nephrol. 2014;2014:574261. doi: 10.1155/2014/574261. Epub 2014 Mar 26.

The novel diagnostic biomarkers for focal segmental glomerulosclerosis.

Author information

1
Department of Nephrology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran 1666694516, Iran ; Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3
Clinical Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden ; SciLifeLab, Stockholm, Sweden.

Abstract

BACKGROUND:

Focal segmental glomerulosclerosis (FSGS) is a glomerular injury with various pathogenic mechanisms. Urine proteome panel might help in noninvasive diagnosis and better understanding of pathogenesis of FSGS.

METHOD:

We have analyzed the urine sample of 11 biopsy-proven FSGS subjects, 8 healthy controls, and 6 patients with biopsy-proven IgA nephropathy (disease controls) by means of liquid chromatography tandem mass spectrometry (nLC-MS/MS). Multivariate analysis of quantified proteins was performed by principal component analysis (PCA) and partial least squares (PLS).

RESULTS:

Of the total number of 389 proteins, after multivariate analysis and additional filter criterion and comparing FSGS versus IgA nephropathy and healthy subjects, 77 proteins were considered as putative biomarkers of FSGS. CD59, CD44, IBP7, Robo4, and DPEP1 were the most significant differentially expressed proteins. These proteins are involved in pathogenic pathways: complement pathway, sclerosis, cell proliferation, actin cytoskeleton remodeling, and activity of TRPC6.There was complete absence of DPEP1 in urine proteome of FSGS subjects compared with healthy and disease controls. DPEP1 acts via leukotrienes on TRPC6 and results in increased podocyte motility and proteinuria.

CONCLUSION:

The results suggest a panel of candidate biomarkers for noninvasive diagnosis of FSGS, while complete absence of DPEP1 might represent a novel marker of FSGS.

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