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Titolo:
Macrophage-derived MTI-MMP and increased MMP-2 activity are associated with glomerular damage in crescentic glomerulonephritis
Autore:
Hayashi, K; Horikoshi, S; Osada, S; Shofuda, K; Shirato, I; Tomino, Y;
Indirizzi:
Juntendo Univ, Sch Med, Div Nephrol, Dept Med,Bunkyo Ku, Tokyo 1138421, Japan Juntendo Univ Tokyo Japan 1138421 pt Med,Bunkyo Ku, Tokyo 1138421, Japan TERUMO R&D Ctr, Inst Biomed Sci, Kanagawa, Japan TERUMO R&D Ctr KanagawaJapan R&D Ctr, Inst Biomed Sci, Kanagawa, Japan
Titolo Testata:
JOURNAL OF PATHOLOGY
fascicolo: 3, volume: 191, anno: 2000,
pagine: 299 - 305
SICI:
0022-3417(200007)191:3<299:MMAIMA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYPE-1 MATRIX METALLOPROTEINASE; FIBRONECTIN MESSENGER-RNA; BASEMENT-MEMBRANE DISEASE; IN-SITU HYBRIDIZATION; PRO-GELATINASE-A; EXTRACELLULAR-MATRIX; TRANSMEMBRANE DOMAIN; ENHANCED EXPRESSION; GLOMERULOSCLEROSIS; TISSUE;
Keywords:
MT1-MMP; MMP-2; ISH; macrophage; crescentic glomerulonephritis; anti-GBM antibody; rat model;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Tomino, Y Juntendo Univ, Sch Med, Div Nephrol, Dept Med,Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan Juntendo Univ 2-1-1 Hongo Tokyo Japan 1138421 yo 1138421, Japan
Citazione:
K. Hayashi et al., "Macrophage-derived MTI-MMP and increased MMP-2 activity are associated with glomerular damage in crescentic glomerulonephritis", J PATHOLOGY, 191(3), 2000, pp. 299-305

Abstract

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-GEM 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 reachedmaximum 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. Usingan 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 immunostainingof 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. Copyright (C) 2000 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 22:35:22