Matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients with various glomerular diseases and their implication in pathogenetic lesions: Study based on an enzyme-linked assay and immunohistochemical staining

被引：21
作者：
Endo T. [1 ]
Nakabayashi K. [1 ]
Sekiuchi M. [1 ]
Kuroda T. [1 ]
Soejima A. [1 ]
Yamada A. [1 ]
机构：
[1] First Department of Internal Medicine, Kyorin University, School of Medicine, Mitaka, Tokyo 181-8611
来源：
Clinical and Experimental Nephrology | 2006年 / 10卷 / 4期
关键词：
Glomerulonephritis; Metalloproteinase; Tissue inhibitor of metalloproteinase;
D O I：
10.1007/s10157-006-0438-3
中图分类号：
学科分类号：
摘要：
Background. Various glomerular diseases progress to end-stage renal failure due to an accumulation of the mesangial matrix (MM) and a thickening of the glomerular basement membrane (GBM). Both the MM and GBM are consistently metabolized through the synthesis and destruction of the matrix. Such synthesis is influenced by transforming growth factor-β (TGF-β) and other factors, whereas the destruction is presumed to be mediated by both matrix metalloproteinases (MMPs) and inhibitors of matrix metalloproteinases (TIMPs). Based on such evidence, we tried to detect MMP-2, MMP-9, and TIMP-1 in the peripheral blood of patients with various glomerular diseases. Methods. Serum was used to detect MMP-2 and TIMP-1, while plasma was used to detect MMP-9. These enzymes were detected using an enzyme-linked assay. Results. The findings showed an increased level of MMP-2 in patients with a alteration of GBM, typically membranous nephropathy (MN), regardless of the differences in their etiological processes. In contrast, MMP-9 did not show a strong association with any specific glomerular abnormalities. However, it mainly tended to increase in patients with MM accumulation. In addition, the localization of MMP-2, MMP-9, and TGF-β1 was studied using immunohistochemical staining. MMP-2 was demonstrated to exist in the glomerular capillary loop (GCL) as well as in the mesangial cells and the mesangial matrix. MMP-9 was found to exist in mesangial cells and the matrix, GCL, infiltrated neutrophils, and some tubular epithelial cells. Positive staining for TGF-β1 in GCL was found to be associated with an increased level of MMP-2 in patients with MN, whereas in MM such positive staining was not necessarily associated with an increased level of MMP-9. Conclusions. These results therefore suggest that MMP-2 plays an important role in the degradation of GBM, while MMP-9 only moderately affects the degradation of MM. © 2006 Japanese Society of Nephrology.
引用
收藏
页码：253 / 261
页数：8
相关论文
共 28 条
  • [11] Jalalah S.M., Furness P.N., Barker G., Thomas M., Hall L., Bicknell G.R., Et al., Inactive matrix metalloproteinase 2 is a normal constituent of human glomerular basement membrane. An immuno-electron microscopic study, J Pathol, 191, pp. 61-6, (2000)
  • [12] Kanauchi M., Nishioka H., Nakashima Y., Hashimoto T., Dohi K., Role of tissue inhibitors of metalloproteinase in diabetic nephropathy, Jpn J Nephrol, 38, pp. 124-8, (1996)
  • [13] Akiyama K., Shikata K., Sugimoto H., Matsuda M., Shikata Y., Fujimoto N., Et al., Changes in serum concentration of matrix metalloproteinases and type IV collagen in patients with various types of glomerulonephritis, Res Commun Mol Pathol Pharmacol, 95, pp. 115-28, (1997)
  • [14] Waku A., Nakabayashi K., Karube M., Nagasawa T., Serum TIMP-1 level in various glomerulonephritides (in Japanese, with English abstract), Kyorin J Med Sci, 28, pp. 441-7, (1997)
  • [15] Fujimoto N., Iwata K., Enzyme immunoassays for matrix metalloproteinases and their inhibitors, Connect Tissue, 26, pp. 237-44, (1994)
  • [16] Tomino Y., Sakai H., Special Study Group (IgA nephropathy) on progressive glomerular disease: Clinical guidelines for immunoglobulin a (IgA) nephropathy in Japan, 2nd version, Clin Exp Nephrol, 7, pp. 93-7, (2003)
  • [17] Ehreinreich T., Churg J., Pathology of membranous nephropathy, Annual Review of Pathology 1968, 3, pp. 145-148, (1968)
  • [18] Border W.A., Noble N.A., Transforming growth factor β in tissue fibrosis, N Engl J Med, 331, pp. 1286-92, (1994)
  • [19] Daly L.E., Bourke G.J., Comparisons of two independent medians, Interpretation and Uses of Medical Statistics, 5th Ed., pp. 218-221, (2000)
  • [20] Daly L.E., Bourke G.J., Associations between two quantitative variables: Regression and correlation, Interpretation and Uses of Medical Statistics, 5th Ed., pp. 315-338, (2000)
123