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.
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-beta (TGF-beta) 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-beta1 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-beta1 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.
Endo
Tetsuya
T
First Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
Nakabayashi
Kimimasa
K
Sekiuchi
Makiho
M
Kuroda
Tadahide
T
Soejima
Akinori
A
Yamada
Akira
A
D004797:Enzyme-Linked Immunosorbent Assay; D050533:Glomerular Basement Membrane / Q000737:chemistry; D005921:Glomerulonephritis / Q000097:blood* / Q000503:physiopathology; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D053773:Transforming Growth Factor beta1 / Q000097:blood
D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9