gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Matrix Metalloproteinases and their Regulators in a Rat Model of Angiotensin II-dependent Nephropathy

Matrix Metalloproteinasen und ihre Regulatoren in einem Rattenmodell mit Angiotensin-II-abhängiger Nephropathie

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker J. Bolbrinker - Charité - Universitätsmedizin Berlin (Berlin, D)
  • S. Markovic - Charité - Universitätsmedizin Berlin (Berlin, D)
  • P. Kossmehl - Charité - Universitätsmedizin Berlin (Berlin, D)
  • M. Wehland - Charité - Universitätsmedizin Berlin (Berlin, D)
  • R. Kreutz - Charité - Universitätsmedizin Berlin (Berlin, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP6

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch106.shtml

Veröffentlicht: 11. November 2004

© 2004 Bolbrinker et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Accumulation of extracellular matrix (ECM) in the glomerular mesangium is common to a variety of progressive renal diseases and matrix metalloproteinases (MMP) are known to be the major physiologic regulators of ECM degradation in the glomerulus. Angiotensin II (AngII) plays an important role in the proliferation of mesangial cells (MC) as well as in the synthesis of ECM components. We therefore investigated the expression of MMP-2 and MMP-9 genes as well as the expression of their endogenous inhibitors, namely tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2 in isolated glomeruli of male homozygous TGR (mRen2) 27 (TGR) and Sprague-Dawley (SD) rats (n=9, respectively). Determination of the glomerular sclerosis index (GSI) revealed a significant increase of GSI in the transgenic rats (p<0.01). Quantification of MMP-2 and MMP-9 mRNA levels by real-time RT-PCR using the TaqMan-technology showed an 80% increase in MMP-2 mRNA (p<0.05) and a 90% decrease of MMP-9 compared to SD (p<0.01). TIMP-1 mRNA increased to 207% (p<0.01), whereas TIMP-2 showed no significant difference between the transgenic rats and SD. In contrast, exposure of primary cultured rat MC to AngII (1µM) for 8h, 12h and 24h led to a transient 40% increase of MMP-9 mRNA levels after 8h (p<0.05) and to a 50% decrease of MMP-2 after 24h (p<0.01). In accordance to the in vivo data, TIMP-1 levels were significantly upregulated after 12h whereas TIMP-2 expression was not altered by AngII treatment. Downregulation of MMP-9 and increase of MMP-2 and TIMP-1 mRNA in isolated glomeruli of transgenic rats showing signs of renal damage as a result of AngII-dependent hypertension was shown. The observed discrepancy of MMP-9 and MMP-2 expression between the in vitro and in vivo data may either be due to the chronicity of elevated AngII-levels in the in vivo situation or might be explained by the involvement of AngII-independent molecular mechanisms leading to altered expression of MMP in vivo.