title: The novel diagnostic biomarkers for focal segmental glomerulosclerosis.
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.
authors.affiliation: 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.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nafar
authors.affiliation: Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shiva
authors.identifier: 0000-0001-7690-141X
authors.initials: S
authors.lastname: Kalantari
authors.affiliation: 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.
authors.forename: Shiva
authors.identifier: 0000-0001-6707-7844
authors.initials: S
authors.lastname: Samavat
authors.affiliation: Clinical Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Rezaei-Tavirani
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden ; SciLifeLab, Stockholm, Sweden.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Rutishuser
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden ; SciLifeLab, Stockholm, Sweden.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zubarev