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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-11-21
pubmed:abstractText
Membrane-type matrix metalloproteinases (MT-MMPs) have been shown to activate pro-MMP-2 on the cell surface and are suggested to be key enzymes in tissue remodelling under various physiological and pathological conditions. To investigate the role of MT-MMP in progressive renal injury, the gene expression and enzymatic activity of MT-MMP were examined in crescentic glomerulonephritis induced by anti-glomerular basement membrane (GBM) antibody in WKY rats. Isolated glomeruli were subjected to RNA and protein extraction 0, 1, 3, 7, 14, and 28 days after intravenous injection of rabbit anti-GBM antibody. Semiquantitative RT-PCR analysis revealed that among the three members of the MT-MMP family, mRNA expression of MT2-MMP remained unchanged and that of MT3-MMP was not observed in glomeruli during the development of nephritis. However, MT1-MMP gene expression increased from day 3 and reached maximum levels at day 7 (5.5+/-0.7-fold increase over day 0), closely associated with macrophage accumulation, crescent formation, and increased proteinuria. Gelatin zymography showed that the active from of MMP-2 emerged from day 7 and remained during the experimental period accompanied by increased proMMP-2, while no active form of MMP-2 was found in control rats. Using an antisense cRNA probe, intense signals of MT1-MMP mRNA were observed mostly in cells within the crescent and in some cells in the mesangial areas. Most of these cells were ED-1-positive macrophages, based on immunostaining of sequential sections. These results suggested that in the MT-MMP family, MT1-MMP was induced in infiltrating macrophages during the development of crescentic glomerulonephritis and possibly contributed to pathological degradation of glomerular extracellular matrices through the activation of proMMP-2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright 2000 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
191
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
299-305
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10878552-Animals, pubmed-meshheading:10878552-Autoimmune Diseases, pubmed-meshheading:10878552-Disease Models, Animal, pubmed-meshheading:10878552-Disease Progression, pubmed-meshheading:10878552-Extracellular Matrix, pubmed-meshheading:10878552-Gene Expression, pubmed-meshheading:10878552-Glomerulonephritis, pubmed-meshheading:10878552-Macrophages, pubmed-meshheading:10878552-Male, pubmed-meshheading:10878552-Matrix Metalloproteinase 2, pubmed-meshheading:10878552-Matrix Metalloproteinases, Membrane-Associated, pubmed-meshheading:10878552-Metalloendopeptidases, pubmed-meshheading:10878552-RNA, Messenger, pubmed-meshheading:10878552-Rabbits, pubmed-meshheading:10878552-Rats, pubmed-meshheading:10878552-Rats, Inbred WKY, pubmed-meshheading:10878552-Tissue Inhibitor of Metalloproteinase-2
pubmed:year
2000
pubmed:articleTitle
Macrophage-derived MT1-MMP and increased MMP-2 activity are associated with glomerular damage in crescentic glomerulonephritis.
pubmed:affiliation
Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
pubmed:publicationType
Journal Article