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：29

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

页码：253 / 261

页数：8

共 28 条

[1]

Schnapper H.W., Balance between matrix synthesis and degradation: A determinant of glomerulosclerosis, Pediatr Nephrol, 9, pp. 104-11, (1995)

[2]

Weber M., Basement membrane proteins, Kidney Int, 41, pp. 620-8, (1992)

[3]

Davis M., Martin J., Thomas G.J., Lovett D.H., Proteinases and glomerular matrix turnover, Kidney Int, 41, pp. 671-8, (1992)

[4]

Lenz O., Elliot S.J., Stetler-Stevenson W.G., Matrix metalloproteinases in renal development and disease, J Am Soc Nephrol, 11, pp. 574-81, (2000)

[5]

Osawa H., Yamabe H., Kaizuka M., Nakamura N., Shirato K., Sugawara T., Et al., Platelet-derived growth factor stimulates matrix metalloproteinase-2 secretion in cultured human mesangial cells, Clin Exp Nephrol, 6, pp. 202-6, (2002)

[6]

Kuroda T., Yoshida Y., Kamiie J., Kovalenko P., Nammeta M., Fujinaka H., Et al., Expression of MMP-9 in mesangial cells and its changes in anti-GBM glomerulonephritis in WKY rats, Clin Exp Nephrol, 8, pp. 206-15, (2004)

[7]

Sternlicht M.D., Werb Z., Kreis T., Vale R., Gelatinases (MMPs 2 and 9), Guidebook to the Extracellalar Matrix, Anchor, and Adhesion Proteins 2nd Ed., pp. 529-31, (1999)

[8]

McMillan J.I., Riordan J.W., Couser W.G., Pollock A.S., Lovett D.H., Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy, J Clin Invest, 47, pp. 1094-101, (1966)

[9]

Sato Y., Fujimoto S., Hamai K., Eto T., Serial alterations of glomerular matrix-degrading metalloproteinase activity in anti-thymocyte-induced glomerulonephritis in rats, Nephron, 78, pp. 195-200, (1998)

[10]

Steinmann-Niggil K., Ziswiler R., Kung M., Marti H.P., Inhibition of matrix metalloproteinases attenuates anti-Thy 1.1 nephritis, J Am Soc Nephrol, 9, pp. 397-407, (1998)

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