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

• 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: Hindawi Limited 2018-01-01
• Series: Journal of Diabetes Research
• Online Access: http://dx.doi.org/10.1155/2018/6165303
• ISSN: 2314-6745; 2314-6753

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.