Matrix Metalloproteinase-2 Dysregulation in Type 1 Diabetes

Overview

Journal Diabetes Care

Specialty Endocrinology

Date 2007 Jun 15

PMID 17563344

Citations 54

Authors

Kathryn M Thrailkill

Robert C Bunn

Cynthia S Moreau

Gael E Cockrell

Pippa M Simpson

Hannah N Coleman

J Paul Frindik

Stephen F Kemp

John L Fowlkes

Affiliations

Soon will be listed here.

Abstract

Objective: Dysregulation of matrix metalloproteinase (MMP)-2 may contribute pathologically to the development of diabetes complications, including diabetic retinopathy and coronary and peripheral arterial disease. Our objective was to explore whether systemic MMP-2 dysregulation could be demonstrated in type 1 diabetes and to determine how MMP-2 concentration relates to disease status.

Research Design And Methods: In this cross-sectional study, MMP-2 concentrations and MMP-2 activity were measured in plasma and timed urine samples from 93 type 1 diabetic and 50 healthy control subjects, aged 14-40 years. Relationships between MMP-2 concentrations in these biological fluids and subject characteristics (sex, age, and duration of type 1 diabetes), indexes of glycemic control (A1C, fasting plasma glucose, and continuous glucose monitoring system average daily glucose), and measurements of renal function (urinary albumin excretion and glomerular filtration rate) were examined.

Results: Urine and plasma MMP-2 concentrations and plasma MMP-2 activity were all significantly elevated in type 1 diabetic subjects compared with those in control subjects. Urine MMP-2 concentrations, in particular, were correlated with several clinical parameters that infer increased risk for diabetic comorbidity and specifically for diabetic nephropathy, including higher A1C, longer duration of disease, evidence of renal hyperfiltration, and the presence of microalbuminuria.

Conclusions: Urine and plasma MMP-2 concentrations are dysregulated in type 1 diabetes; urinary excretion of MMP-2, in particular, might provide a unique biomarker of diabetes-induced intrarenal pathologic processes.

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References

Corbel M, Belleguic C, Boichot E, Lagente V . Involvement of gelatinases (MMP-2 and MMP-9) in the development of airway inflammation and pulmonary fibrosis. Cell Biol Toxicol. 2002; 18(1):51-61. DOI: 10.1023/a:1014471213371. View

Asanuma K, Shirato I, Ishidoh K, Kominami E, Tomino Y . Selective modulation of the secretion of proteinases and their inhibitors by growth factors in cultured differentiated podocytes. Kidney Int. 2002; 62(3):822-31. DOI: 10.1046/j.1523-1755.2002.00539.x. View

Noda K, Ishida S, Inoue M, Obata K, Oguchi Y, Okada Y . Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2003; 44(5):2163-70. DOI: 10.1167/iovs.02-0662. View

Visse R, Nagase H . Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003; 92(8):827-39. DOI: 10.1161/01.RES.0000070112.80711.3D. View

Cheng S, Lovett D . Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol. 2003; 162(6):1937-49. PMC: 1868144. DOI: 10.1016/S0002-9440(10)64327-1. View

Hao F, Yu J . High glucose enhance expression of matrix metalloproteinase-2 in smooth muscle cells. Acta Pharmacol Sin. 2003; 24(6):534-8. View

Death A, Fisher E, McGrath K, Yue D . High glucose alters matrix metalloproteinase expression in two key vascular cells: potential impact on atherosclerosis in diabetes. Atherosclerosis. 2003; 168(2):263-9. DOI: 10.1016/s0021-9150(03)00140-0. View

Butterworth B, Eldridge S . A decision tree approach for carcinogen risk assessment. Prog Clin Biol Res. 1995; 391:49-70. View

Chiogna M, Spiegelhalter D, Franklin R, Bull K . An empirical comparison of expert-derived and data-derived classification trees. Stat Med. 1996; 15(2):157-69. DOI: 10.1002/(SICI)1097-0258(19960130)15:2<157::AID-SIM149>3.0.CO;2-5. View

10.

Essawy M, Soylemezoglu O, Shortland J, Brown C, El Nahas A . Myofibroblasts and the progression of diabetic nephropathy. Nephrol Dial Transplant. 1997; 12(1):43-50. DOI: 10.1093/ndt/12.1.43. View

11.

Thrailkill K, Kumar S, Rosenberg C, Auten K, Fowlkes J . Characterization of matrix metalloproteinases in human urine: alterations during adolescence. Pediatr Nephrol. 1999; 13(3):223-9. DOI: 10.1007/s004670050597. View

12.

Romanic A, Burns-Kurtis C, Ao Z, Arleth A, Ohlstein E . Upregulated expression of human membrane type-5 matrix metalloproteinase in kidneys from diabetic patients. Am J Physiol Renal Physiol. 2001; 281(2):F309-17. DOI: 10.1152/ajprenal.2001.281.2.F309. View

13.

Giebel S, Menicucci G, McGuire P, Das A . Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier. Lab Invest. 2005; 85(5):597-607. DOI: 10.1038/labinvest.3700251. View

14.

Signorelli S, Malaponte G, Libra M, Di Pino L, Celotta G, Bevelacqua V . Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease. Vasc Med. 2005; 10(1):1-6. DOI: 10.1191/1358863x05vm582oa. View

15.

Kramer H, Molitch M . Screening for kidney disease in adults with diabetes. Diabetes Care. 2005; 28(7):1813-6. DOI: 10.2337/diacare.28.7.1813. View

16.

Inada A, Nagai K, Arai H, Miyazaki J, Nomura K, Kanamori H . Establishment of a diabetic mouse model with progressive diabetic nephropathy. Am J Pathol. 2005; 167(2):327-36. PMC: 1603579. DOI: 10.1016/s0002-9440(10)62978-1. View

17.

Keeling J, Herrera G . Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Kidney Int. 2005; 68(4):1590-603. DOI: 10.1111/j.1523-1755.2005.00571.x. View

18.

Cherney D, Sochett E, Miller J . Gender differences in renal responses to hyperglycemia and angiotensin-converting enzyme inhibition in diabetes. Kidney Int. 2005; 68(4):1722-8. DOI: 10.1111/j.1523-1755.2005.00588.x. View

19.

Derosa G, Avanzini M, Geroldi D, Fogari R, Lorini R, De Silvestri A . Matrix metalloproteinase 2 may be a marker of microangiopathy in children and adolescents with type 1 diabetes mellitus. Diabetes Res Clin Pract. 2005; 70(2):119-25. DOI: 10.1016/j.diabres.2005.03.020. View

20.

Liu S, Liang Y, Huang H, Wang L, Li Y, Li J . ERK-dependent signaling pathway and transcriptional factor Ets-1 regulate matrix metalloproteinase-9 production in transforming growth factor-beta1 stimulated glomerular podocytes. Cell Physiol Biochem. 2005; 16(4-6):207-16. DOI: 10.1159/000089846. View