基质金属蛋白酶
基底膜
免疫染色
肾小球肾炎
肾小球基底膜
巨噬细胞
肾炎
基因表达
生物
肾
病理
化学
分子生物学
内分泌学
免疫学
免疫组织化学
医学
基因
细胞生物学
体外
生物化学
作者
Kayo Hayashi,Satoshi Horikoshi,Shiwori Osada,Ken‐ichi Shofuda,Isao Shirato,Yasuhiko Tomino
标识
DOI:10.1002/1096-9896(2000)9999:9999<::aid-path637>3.0.co;2-l
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI