MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade

Mora-Gutiérrez, J.M. (José María); Rodriguez, J.A. (José Antonio); Fernández-Seara, M.A. (María A.); Orbe, J. (Josune); Escalada, F.J. (Francisco Javier); Soler, M.J. (María José); Slon-Roblero, M.F. (María Fernanda); Riera, M. (Marta); Paramo, J.A. (José Antonio); Garcia-Fernandez, N. (Nuria)

Issue Date:

2020

Project:

info:eu-repo/grantAgreement/MINECO/Proyectos de investigación en salud (Modalidad proyectos de investigación en salud) (AES 2015)/PI15%2F02111/ES/Estudio clínico y experimental del papel de la MMP-10 en la nefropatía diabética tipo 2

ISSN:

2045-2322

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Citation:

Mora-Gutiérrez, J.M. (José María); Rodriguez, J.A. (José Antonio); Fernández-Seara, M.A. (María A.); et al. "MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade". Scientific Reports. 10 (26), 2020,

Abstract

Matrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473±274pg/ml vs. 332±151; p=0.02) and TIMP-1 (573±296ng/ml vs. 375±317; p<0.001) levels were signifcantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to endstage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and signifcant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.

URI:

https://hdl.handle.net/10171/67154

DOI:

10.1038/s41598-019-56856-3

Appears in Collections:

DA - CIMA - Enfermedades cardiovasculares - Aterosclerosis e inflamación - Artículos de revista
DA - CUN - Endocrinología y Nutrición - Artículos de revista
DA - CUN - Nefrología - Artículos de revista
DA - CUN - Radiología - Artículos de revista

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