Article

Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis.

Department of Medicine, Inselspital Bern, Switzerland.
Journal of the American Society of Nephrology (impact factor: 9.66). 03/1998; 9(3):397-407. pp.397-407
Source: PubMed

ABSTRACT There is accumulating evidence that matrix metallo-proteinases (MMP) play a prominent role in glomerular inflammatory diseases. The aim of the present study was to determine the anti-inflammatory effects of the synthetic MMP inhibitor BB-1101 in acute anti-Thy1.1 nephritis. Sixty-three male Wistar rats were studied: healthy rats (n = 9), treated healthy rats (n = 9), nephritic rats (n = 18), and treated nephritic rats (n = 27). BB-1101 therapy (30 mg/kg body wt per d) of nephritic animals was initiated either 2 d before (n = 18) or 2 d after (n = 9) disease induction. Renal histology was analyzed 11 d after induction of the nephritis, at the peak of MMP-2 production and total glomerular cellularity. Pretreatment of nephritic rats by BB-1101 resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, extracellular matrix deposition, and size of glomerular cross-sections. These beneficial effects were less pronounced, but in part still significant, in animals treated by BB-1101 after induction of anti-Thy1.1 nephritis. Proteinuria, expressed as area under the curve of the protein:creatinine ratio versus time, was clearly decreased in both groups of treated nephritic rats. Healthy control rats were not affected by MMP inhibitor treatment. In summary, the present study demonstrates for the first time in vivo that mesangial cell proliferation can be effectively suppressed by MMP inhibition. Thus, MMP inhibition by synthetic compounds may represent a new approach to the therapy of mesangial cell-mediated forms of glomerulonephritis.

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Keywords

30 mg/kg body wt
 
acute anti-Thy1.1 nephritis
 
anti-inflammatory effects
 
anti-Thy1.1 nephritis
 
extracellular matrix deposition
 
glomerular cellularity
 
glomerular inflammatory diseases
 
glomerulonephritis
 
Healthy control rats
 
healthy rats
 
male Wistar rats
 
mesangial cell proliferation
 
mesangial cell-mediated forms
 
MMP inhibition
 
MMP inhibitor treatment
 
MMP-2 production
 
nephritic rats
 
significant amelioration
 
synthetic MMP inhibitor BB-1101
 
total glomerular cellularity
 

K Steinmann-Niggli