caa a22 4500 475772784 CHVBK 20180406123622.0 cr unu---uuuuu 170329e20000501xx s 000 0 eng 10.1007/s001250051353 doi (NATIONALLICENCE)springer-10.1007/s001250051353 High glucose concentration inhibits the expression of membrane type metalloproteinase by mesangial cells: possible role in mesangium accumulation [Elektronische Daten] [S. V. McLennan, S. Y. K Martell, D. K. Yue] Aims/hypothesis. High glucose concentration decreases the degradation of mesangium matrix, an action substantially mediated by a reduction in the activities of the matrix metalloproteinases (MMPs). Metalloproteinase-2 is unique in that it is activated on the cell surface by one of the membrane type metalloproteinases (MT1-MMP), a process involving complex interactions with tissue inhibitor of metalloproteinase-2. The aim of this study was investigate the effects of glucose concentration on mesangial cell gene expression of MT1-MMP and its ability to modulate the activation of metalloproteinase-2. Methods. Gene expression was determined using competitive RT-PCR, protein expression of MMP-2 was measured by western blot and its activation by zymography. Concanavalin A, known to increase MT1-MMP expression was added in some experiments. Results. High glucose concentration decreased MT1-MMP gene expression (11.52 ± 1.63 and 4.84 ± 0.72 amol/μg RNA, 5 vs 25 mmol/l glucose, respectively) and decreased activation of MMP-2 by 30 % despite a twofold increase in gene expression of MMP-2. Concanavalin A increased expression of MT1-MMP and activation of MMP-2. Irrespective of whether MMP-2 was from endogenous or exogenous source there was an excellent correlation between the MT1-MMP expression and degree of MMP-2 activation, whereas the gene expression of TIMP-2 was not significantly altered by high glucose concentration or concanavalin A. Conclusions/interpretation. Our results indicate that in a high glucose milieu, suppression of MT1-MMP expression could explain the low MMP-2 activity in the presence of high MMP-2 expression. This process could contribute to the mesangium matrix accumulation in diabetic nephropathy. [Diabetologia (2000) 43: 642-648] Springer-Verlag Berlin Heidelberg, 2000 Keywords Matrix metalloproteinase nationallicence nephropathy nationallicence extracellular matrix nationallicence degradation nationallicence McLennan S. V. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia, AU aut Martell S. Y. K. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia, AU aut Yue D. K. Department of Medicine University of Sydney, Sydney, Australia, AU aut https://doi.org/10.1007/s001250051353 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051353 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- McLennan S. V. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia, AU aut NATIONALLICENCE 700 1- Martell S. Y. K. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia, AU aut NATIONALLICENCE 700 1- Yue D. K. Department of Medicine University of Sydney, Sydney, Australia, AU aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer