Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy

Urinary proteome was analyzed and quantified by tandem mass tag (TMT) labeling followed by bioinformatics analysis to study diabetic nephropathy (DN) pathophysiology and to identify biomarkers of a clinical outcome. We included type 2 diabetic normotensive non-obese males with (n=9) and without (n=1...

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Main Authors: Elena Guillén-Gómez, Beatriz Bardají-de-Quixano, Sílvia Ferrer, Carlos Brotons, Mark A. Knepper, Montserrat Carrascal, Joaquin Abian, José M. Mas, Francesca Calero, José A. Ballarín, Patricia Fernández-Llama
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2018/6165303
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author Elena Guillén-Gómez
Beatriz Bardají-de-Quixano
Sílvia Ferrer
Carlos Brotons
Mark A. Knepper
Montserrat Carrascal
Joaquin Abian
José M. Mas
Francesca Calero
José A. Ballarín
Patricia Fernández-Llama
author_facet Elena Guillén-Gómez
Beatriz Bardají-de-Quixano
Sílvia Ferrer
Carlos Brotons
Mark A. Knepper
Montserrat Carrascal
Joaquin Abian
José M. Mas
Francesca Calero
José A. Ballarín
Patricia Fernández-Llama
author_sort Elena Guillén-Gómez
collection DOAJ
description Urinary proteome was analyzed and quantified by tandem mass tag (TMT) labeling followed by bioinformatics analysis to study diabetic nephropathy (DN) pathophysiology and to identify biomarkers of a clinical outcome. We included type 2 diabetic normotensive non-obese males with (n=9) and without (n=11) incipient DN (microalbuminuria). Sample collection included blood and urine at baseline (control and DN basal) and, in DN patients, after 3 months of losartan treatment (DN treated). Urinary proteome analysis identified 166 differentially abundant proteins between controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 between DN-treated patients and controls. The mathematical modeling analysis predicted 80 key proteins involved in DN pathophysiology and 15 in losartan effect, a total of 95 proteins. Out of these 95, 7 are involved in both processes. VCAM-1 and neprilysin stand out of these 7 for being differentially expressed in the urinary proteome. We observed an increase of VCAM-1 urine levels in DN-basal patients compared to diabetic controls and an increase of urinary neprilysin in DN-treated patients with persistent albuminuria; the latter was confirmed by ELISA. Our results point to neprilysin and VCAM-1 as potential candidates in DN pathology and treatment.
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spelling doaj-art-fb86f29967484d1fad3ba5d1a8157e5f2025-08-20T02:22:56ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/61653036165303Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic NephropathyElena Guillén-Gómez0Beatriz Bardají-de-Quixano1Sílvia Ferrer2Carlos Brotons3Mark A. Knepper4Montserrat Carrascal5Joaquin Abian6José M. Mas7Francesca Calero8José A. Ballarín9Patricia Fernández-Llama10Molecular Biology Laboratory, Fundació Puigvert, Barcelona, SpainUniversitat Autònoma de Barcelona, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, SpainMaragall Primary Health Care Center, Barcelona, SpainUniversitat Autònoma de Barcelona, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, SpainEpithelial Systems Biology Laboratory, National Heart, Lung, and Blood Institute (NIH), Bethesda, MD, USAProteomics Laboratory CSIC/UAB, Institut d’Investigacions Biomèdiques de Barcelona (IIBB-CSIC-IDIBAPS), Barcelona, SpainProteomics Laboratory CSIC/UAB, Institut d’Investigacions Biomèdiques de Barcelona (IIBB-CSIC-IDIBAPS), Barcelona, SpainAnaxomics Biotech SL, Barcelona, SpainUniversitat Autònoma de Barcelona, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, SpainUniversitat Autònoma de Barcelona, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, SpainUniversitat Autònoma de Barcelona, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, SpainUrinary proteome was analyzed and quantified by tandem mass tag (TMT) labeling followed by bioinformatics analysis to study diabetic nephropathy (DN) pathophysiology and to identify biomarkers of a clinical outcome. We included type 2 diabetic normotensive non-obese males with (n=9) and without (n=11) incipient DN (microalbuminuria). Sample collection included blood and urine at baseline (control and DN basal) and, in DN patients, after 3 months of losartan treatment (DN treated). Urinary proteome analysis identified 166 differentially abundant proteins between controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 between DN-treated patients and controls. The mathematical modeling analysis predicted 80 key proteins involved in DN pathophysiology and 15 in losartan effect, a total of 95 proteins. Out of these 95, 7 are involved in both processes. VCAM-1 and neprilysin stand out of these 7 for being differentially expressed in the urinary proteome. We observed an increase of VCAM-1 urine levels in DN-basal patients compared to diabetic controls and an increase of urinary neprilysin in DN-treated patients with persistent albuminuria; the latter was confirmed by ELISA. Our results point to neprilysin and VCAM-1 as potential candidates in DN pathology and treatment.http://dx.doi.org/10.1155/2018/6165303
spellingShingle Elena Guillén-Gómez
Beatriz Bardají-de-Quixano
Sílvia Ferrer
Carlos Brotons
Mark A. Knepper
Montserrat Carrascal
Joaquin Abian
José M. Mas
Francesca Calero
José A. Ballarín
Patricia Fernández-Llama
Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy
Journal of Diabetes Research
title Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy
title_full Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy
title_fullStr Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy
title_full_unstemmed Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy
title_short Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy
title_sort urinary proteome analysis identified neprilysin and vcam as proteins involved in diabetic nephropathy
url http://dx.doi.org/10.1155/2018/6165303
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