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

Abstract
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.
AuthorsElena 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
JournalJournal of diabetes research (J Diabetes Res) Vol. 2018 Pg. 6165303 ( 2018) ISSN: 2314-6753 [Electronic] England
PMID29854824 (Publication Type: Journal Article)
Chemical References
  • Biomarkers
  • Proteome
  • Vascular Cell Adhesion Molecule-1
  • Neprilysin
Topics
  • Aged
  • Albuminuria (urine)
  • Biomarkers (urine)
  • Diabetes Mellitus, Type 2 (urine)
  • Diabetic Nephropathies (urine)
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neprilysin (urine)
  • Proteome (metabolism)
  • Proteomics
  • Urinalysis
  • Vascular Cell Adhesion Molecule-1 (urine)

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