TY - JOUR
T1 - Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy
AU - Guillén-Gómez, Elena
AU - Bardají-de-Quixano, Beatriz
AU - Ferrer, Sílvia
AU - Brotons, Carlos
AU - Knepper, Mark A.
AU - Carrascal, Montserrat
AU - Abian, Joaquin
AU - Mas, José M.
AU - Calero, Francesca
AU - Ballarín, José A.
AU - Fernández-Llama, Patricia
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
U2 - 10.1155/2018/6165303
DO - 10.1155/2018/6165303
M3 - Article
C2 - 29854824
SN - 2314-6745
VL - 2018
SP - 6165303
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
ER -
