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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Scientific reports - 10(2020), 1 vom: 08. Jan., Seite 26 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mora-Gutiérrez, José María [VerfasserIn] |
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| Links: |
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| Themen: |
Angiotensin II Type 1 Receptor Blockers |
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| Anmerkungen: |
Date Completed 18.11.2020 Date Revised 10.01.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-019-56856-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM305126814 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Rodríguez, José Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Seara, María A |e verfasserin |4 aut | |
| 700 | 1 | |a Orbe, Josune |e verfasserin |4 aut | |
| 700 | 1 | |a Escalada, Francisco Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Soler, María José |e verfasserin |4 aut | |
| 700 | 1 | |a Slon Roblero, María Fernanda |e verfasserin |4 aut | |
| 700 | 1 | |a Riera, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Páramo, José Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia-Fernandez, Nuria |e verfasserin |4 aut | |
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