Original Paper

Effect of Glucose on Matrix Metalloproteinase Activity in Mesangial Cells
Susan V. McLennan, Dennis K. Yue, John R. Turtle

Department of Medicine, University of Sydney, and Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, N.S.W., Australia

Address of Corresponding Author

Nephron 1998;79:293-298 (DOI: 10.1159/000045052)

  Key Words

• Mesangium degradation
• Matrix metalloproteinase
• Diabetic nephropathy

  Abstract

Mesangial cells are known to secrete matrix metalloproteinases (MMPs). These enzymes play a major role in the degradation and remodelling of extracellular matrix, and alterations in their activity may contribute to the mesangium enlargement of diabetic nephropathy. MMPs are secreted as latent forms which are cleaved in the pericellular environment to form active enzymes. In this study, we used a biosynthetically labelled matrix as substrate and conditioned medium obtained from mesangial cells, as a source of enzymes to investigate the effect of a high glucose concentration on degradative capacity. Inhibitor studies showed that MMPs were responsible for 72.2% of the degradation. A high glucose concentration caused a significant reduction in matrix degradation (low glucose 33.5 ± 5.6%, high glucose 24.2±4.8%). Addition of aminophenyl mercuric acetate to activate latent MMPs increased matrix degradation by 2.3-fold in both low- and high-glucose media, but the decreased degradation caused by a high glucose concentration was still apparent. Activation with plasmin also increased matrix degradation and abolished the effect of the high glucose concentration. Gelatin zymography showed that mesangial cells grown at a low glucose concentration secreted both 72- and 92-kD gelatinases; however, at high glucose concentrations the 92-kD gelatinase was no longer apparent. These results suggest that a high glucose concentration causes a reduction in the amount of MMPs secreted by the mesangial cells. This reduction may contribute to the mesangium enlargement of diabetic nephropathy.

  Author Contacts

Ms. S. McLennan
Department of Medicine
University of Sydney
Sydney, NSW 2006 (Australia)
Tel. +61 (2) 9515 6150, Fax +61 (2) 9516 1273

  Article Information

Accepted: February 3, 1998
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 1, Number of References : 22