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

Autor: Mora-Gutiérrez JM; Nephrology Department, Clínica Universidad de Navarra, Pamplona, Spain., Rodríguez JA; Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA, University of Navarra, Pamplona, Spain.; CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Fernández-Seara MA; Radiology Department, Clínica Universidad de Navarra, Pamplona, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Orbe J; Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA, University of Navarra, Pamplona, Spain.; CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Escalada FJ; Endocrinology and Nutrition Department, Clínica Universidad de Navarra, Pamplona, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain., Soler MJ; Nephrology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, Madrid, Spain., Slon Roblero MF; Nephrology Department, Hospital de Navarra, Pamplona, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Riera M; Nephrology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain., Páramo JA; Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA, University of Navarra, Pamplona, Spain.; CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain., Garcia-Fernandez N; Nephrology Department, Clínica Universidad de Navarra, Pamplona, Spain. nrgarcia@unav.es.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. nrgarcia@unav.es.; Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, Madrid, Spain. nrgarcia@unav.es.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Jan 08; Vol. 10 (1), pp. 26. Date of Electronic Publication: 2020 Jan 08.
DOI: 10.1038/s41598-019-56856-3
Abstrakt: 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.
Databáze: MEDLINE
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