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

• Published in: Scientific reports Vol. 10; no. 1; p. 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.01.2020; Nature Publishing Group
• Subjects: 13/1; 38/77; 692/163/2743/137/138; 692/4022/272/1684/1587/2101; 82/51; 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-56856-3

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 < 0.001) levels were significantly 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 end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant 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.