Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis. 951 1

Matrix metalloproteinase-2 (MMP-2, gelatinase A) is involved in the inflammatory and sclerotic events of glomerular diseases. Newly identified membrane-type matrix metalloproteinases (MT-MMP) have been shown to activate specifically proMMP-2. To date, several types of MT-MMP have been cloned; however, their expressions in glomerular diseases have not been evaluated. To investigate the role of MT-MMP in glomerular diseases, the glomerular gene expression and enzymatic activity of MT-MMP were examined during the time course of nephritis induced in rats by anti-Thy1.1 antibody injection. Both MT1-MMP and MMP-2 mRNA expression increased prominently 5 and 10 d after anti-Thy1.1 antibody injection and decreased thereafter, as assayed by semiquantitative reverse transcription-PCR. In contrast, there were no remarkable changes in the gene expression of MT2-MMP between normal and diseased tissue, and that of MT3-MMP was not detected in isolated glomeruli by reverse transcription-PCR analysis. The activation of proMMP-2 as analyzed by gelatin zymography correlated with the glomerular MT1-MMP gene expression, suggesting that proMMP-2 was activated by MT1-MMP. Protein and mRNA expression of fibronectin, one of the major mesangial matrix proteins and substrate of MMP-2, were also synchronized with MT1-MMP and MMP-2 expression. In situ hybridization revealed intense MT1-MMP mRNA expression in the proliferating mesangial cells. Interestingly, MT1-MMP gene expression exhibited a similar distribution as alpha-smooth muscle actin expression, which was closely associated with mesangial phenotypic change. These results suggest that among the newly identified MT-MMP, MT1-MMP may play the central role in activation of proMMP-2. Furthermore, the enhancement of MT1-MMP and MMP-2 expression associated with mesangial phenotypic change may contribute to the development of anti-Thy1.1 antibody-induced glomerulonephritis and remodeling of extracellular matrices.
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PMID:Enhanced expression of membrane type-1 matrix metalloproteinase in mesangial proliferative glomerulonephritis. 984 80