The Novel Diagnostic Biomarkers for Focal Segmental Glomerulosclerosis

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 h...

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Published inInternational Journal of Nephrology Vol. 2014; no. 2014; pp. 123 - 132
Main Authors Nafar, Mohsen, Kalantari, Shiva, Samavat, Shiva, Rezaei-Tavirani, Mostafa, Rutishuser, Dorothea, Zubarev, Roman A.
Format Journal Article
LanguageEnglish
Published Cairo, Egypt Hindawi Limiteds 01.01.2014
Hindawi Puplishing Corporation
Hindawi Publishing Corporation
John Wiley & Sons, Inc
Wiley
Subjects
Age
Apoptosis
Biological markers
Biomarkers
Biopsy
Chromatography
Disease
Enzymes
Immunoglobulin A
Inflammation
Liquid chromatography
Mass spectrometry
Nephrology
Pathogenesis
Proteins
Proteomics
Rodents
Scientific imaging
Software
Studies
Urine
Online AccessGet full text
ISSN2090-2158
2090-214X
2090-2158
DOI10.1155/2014/574261

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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.
AbstractList 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.
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.
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.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.
Audience Academic
Author Kalantari, Shiva
Zubarev, Roman A.
Nafar, Mohsen
Rezaei-Tavirani, Mostafa
Rutishuser, Dorothea
Samavat, Shiva
AuthorAffiliation 2 Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Clinical Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6 Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
7 SciLifeLab, Stockholm, Sweden
3 Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
1 Department of Nephrology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran 1666694516, Iran
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– name: 6 Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
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Copyright Copyright © 2014 Mohsen Nafar et al.
COPYRIGHT 2014 John Wiley & Sons, Inc.
Copyright © 2014 Mohsen Nafar et al. Mohsen Nafar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright © 2014 Mohsen Nafar et al. 2014
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– notice: Copyright © 2014 Mohsen Nafar et al. 2014
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Snippet Background. Focal segmental glomerulosclerosis (FSGS) is a glomerular injury with various pathogenic mechanisms. Urine proteome panel might help in noninvasive...
Background . Focal segmental glomerulosclerosis (FSGS) is a glomerular injury with various pathogenic mechanisms. Urine proteome panel might help in...
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StartPage 123
SubjectTerms Age
Apoptosis
Biological markers
Biomarkers
Biopsy
Chromatography
Disease
Enzymes
Immunoglobulin A
Inflammation
Liquid chromatography
Mass spectrometry
Nephrology
Pathogenesis
Proteins
Proteomics
Rodents
Scientific imaging
Software
Studies
Urine
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Title The Novel Diagnostic Biomarkers for Focal Segmental Glomerulosclerosis
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https://dx.doi.org/10.1155/2014/574261
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