Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis.
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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ABSTRACT: Not Available Bibtex entry for this abstract Preferred format for this abstract (see Preferences) Find Similar Abstracts: Use: Authors Title Return: Query Results Return items starting with number Query Form Database: Astronomy Physics arXiv e-printsPLoS ONE 01/2008; 3(5). · 3.53 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) are important enzymes of extracellular matrix (ECM) degradation for creating the cellular environments required during development and morphogenesis. MMPs, collectively called matrixins, regulate also the biological activity of non matrix substrates such as cytokines, chemokines, receptors, growth factors and cell adhesion molecules. Enzymatic activity is regulated at multiple levels. Endogenous specific inhibitors of metalloproteinases (TIMPs) participate in controlling the local activities of MMPs in tissues. The pathological effects of MMPs and TIMPs are involved in cardiovascular disease (CVD) processes, including atherosclerosis and in a number of renal pathophysiologic alterations, both acute and chronic, linking them to acute kidney injury, glomerulosclerosis and tubulointerstitial fibrosis. This review presents an overview of the place of MMPs in atherosclerosis, proteinuria and kidney disease as a subject of considerable interest, given the differentiated and ambiguous role of MMPs in the progression of these diseases.Hippokratia 10/2013; 17(4):292-7. · 0.59 Impact Factor