MMP-10 is increased in early stage diabetic kidney disease and can be reduced by renin-angiotensin system blockade
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- dc.contributor.author Mora-Gutiérrez, José María
- dc.contributor.author Rodríguez, José Antonio
- dc.contributor.author Fernández-Seara, María A.
- dc.contributor.author Orbe, Josune
- dc.contributor.author Escalada, Francisco Javier
- dc.contributor.author Soler, María José
- dc.contributor.author Slon Roblero, María Fernanda
- dc.contributor.author Riera Oliva, Marta
- dc.contributor.author Páramo, José Antonio
- dc.contributor.author García-Fernández, Nuria
- dc.date.accessioned 2020-06-22T06:33:31Z
- dc.date.available 2020-06-22T06:33:31Z
- dc.date.issued 2020
- dc.description.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 ± 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Mora-Gutiérrez JM, Rodríguez JA, Fernández-Seara MA, Orbe J, Escalada FJ, Soler MJ, et al. MMP-10 is increased in early stage diabetic kidney disease and can be reduced by renin-angiotensin system blockade. Sci Rep. 2020 Jan 8; 10(1):26. DOI: 10.1038/s41598-019-56856-3
- dc.identifier.doi http://dx.doi.org/10.1038/s41598-019-56856-3
- dc.identifier.issn 2045-2322
- dc.identifier.uri http://hdl.handle.net/10230/45022
- dc.language.iso eng
- dc.publisher Nature Research
- dc.rights Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Ronyons -- Malalties
- dc.subject.other Diabetis
- dc.subject.other MMP-10
- dc.title MMP-10 is increased in early stage diabetic kidney disease and can be reduced by renin-angiotensin system blockade
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion