Journal Article

Glomerular distribution and gelatinolytic activity of matrix metalloproteinases in human glomerulonephritis

Maki Urushihara, Shoji Kagami, Takashi Kuhara, Toshiaki Tamaki and Yasuhiro Kuroda

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 17, issue 7, pages 1189-1196
Published in print July 2002 | ISSN: 0931-0509
Published online July 2002 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/17.7.1189
Glomerular distribution and gelatinolytic activity of matrix metalloproteinases in human glomerulonephritis

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Background. Matrix metalloproteinases (MMPs) have been implicated in the development of glomerular injury in rat experimental glomerulonephritis (GN). However, the significance of MMPs in human GN remains obscure. In order to evaluate the role of MMPs in human GN, we examined the glomerular distribution and gelatinolytic activities of MMP‐2 and MMP‐9 in human GN.

Methods. We performed immunohistochemistry with polyclonal anti‐MMP‐2 and MMP‐9 antibodies, and analysed gelatin zymograms of five isolated glomeruli from various types of human renal disease. The renal specimens investigated were from normal kidneys (n=5), IgA nephritis (n=20), Henoch–Schönlein nephritis (n=4), non‐IgA mesangial proliferative GN (n=9), lupus nephritis (n=6), acute poststreptococcal GN (APSGN) (n=4) and diabetic nephropathy (DN) (n=4).

Results. MMP‐2 immunoreactivity was not detected in normal controls or in any type of GN. MMP‐9 staining, which was almost negative in normal glomeruli, was increased mainly in the mesangial region and corresponded to the level of glomerular cell proliferative changes in mesangial proliferative GN (IgA nephritis, Henoch–Schönlein nephritis, non‐IgA mesangial proliferative GN and lupus nephritis). Positive but weak staining for MMP‐9 was observed in mesangial areas in DN. In addition, double immunostaining showed that MMP‐9 is colocalized in scattered neutrophils within diseased glomeruli in APSGN. MMP‐9 gelatinolytic activity in five normal glomeruli was weakly detected. Consistent with the levels of immunostaining, MMP‐9 glomerular activity was dramatically increased in nephritic glomeruli with IgA nephritis, lupus nephritis and DN. The gelatinolytic activity of MMP‐2 was occasionally detectable in nephritic glomeruli.

Conclusion. These results strongly suggest that MMP‐9 plays an important role in abnormal mesangial proliferative changes in human GN.

Keywords: gelatin zymograms; human glomerulonephritis; immunohistochemistry; matrix metalloproteinases

Journal Article.  4419 words.  Illustrated.

Subjects: Nephrology

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