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

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 earl...

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Bibliographic Details
Published in:Scientific reports 2020-01, Vol.10 (1), p.26-26, Article 26
Main Authors: Mora-Gutiérrez, José María, Rodríguez, José Antonio, Fernández-Seara, María A., Orbe, Josune, Escalada, Francisco Javier, Soler, María José, Slon Roblero, María Fernanda, Riera, Marta, Páramo, José Antonio, Garcia-Fernandez, Nuria
Format: Article
Language:English
Subjects:
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ACE inhibitors
Aged
Angiotensin
Angiotensin II
Angiotensin II Type 1 Receptor Blockers - pharmacology
Animal models
Animals
Case-Control Studies
Cross-Sectional Studies
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Type 2 - complications
Diabetic Nephropathies - drug therapy
Diabetic Nephropathies - enzymology
Diabetic Nephropathies - etiology
Diabetic nephropathy
End-stage renal disease
Female
Humanities and Social Sciences
Humans
Kidney diseases
Kidneys
Male
Matrix metalloproteinase
Matrix Metalloproteinase 10 - chemistry
Matrix Metalloproteinase 10 - metabolism
Mice
Mice, Inbred C57BL
Microvasculature
Middle Aged
multidisciplinary
Prognosis
Renin
Renin-Angiotensin System - drug effects
Science
Science (multidisciplinary)
Stromelysin 2
Telmisartan - pharmacology
Tissue inhibitor of metalloproteinase 1
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Summary: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 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-56856-3