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NDT Advance Access published online on November 3, 2006

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl618
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received March 4, 2006
Accepted August 26, 2006


Original Article

The expression of matrix metalloproteinase-11 protein in various types of glomerulonephritis

Lydia Nakopoulou 1 *, Andreas C. Lazaris 1, Ioannis Boletis 2, Spyros Michail 2, Christos Iatrou 3, Gabriel Papadakis 4, Sophia Athanassiadou 1, and Charalambos Stathakis 2

1 2nd Department of Pathology, "Attikon" University Hospital, School of Medicine, The National and Kapodistrian University of Athens, Greece
2 Department of Nephrology, "Laikon" General Hospital of Athens, Greece
3 Department of Nephrology, General Regional Hospital of Nikea, Piraeus, Greece
4 Department of Nephrology, "Tzanio" Regional General Hospital of Piraeus, Greece

* To whom correspondence should be addressed.
Lydia Nakopoulou, E-mail: lnakopou{at}cc.uoa.gr



  Abstract

Background. Matrix metalloproteinases (MMPs) have been implicated to play important roles in a number of pathological processes such as inflammation. In human glomeruli, the mesangial matrix turnover is controlled by a dynamic equilibrium between synthesis and degradation to which metalloproteinases are known to contribute. Metalloproteinase-11 (MMP-11) was originally discovered as a gene whose expression was associated with tissue remodelling. The aim of this study was to investigate whether MMP-11 protein is expressed in various types of glomerulonephritis and to elucidate the role of this expression.

Methods. Using standard immunohistochemistry, we analysed MMP-11 expression in renal biopsies from 95 patients with primary glomerulonephritis (n = 44) and secondary, either lupus-associated glomerulonephritis (n = 22) or pauci-immune, ANCA-associated glomerulonephritis due to small vessel vasculitis (n = 23) or Wegener's granulomatosis (n = 6). The examined cases were divided into two groups (proliferative and non-proliferative). Anti-Ki67 and -CD68 immunostaining was also performed in order to estimate cell proliferation and number of macrophages, respectively.

Results. MMP-11 immunopositivity was detected in the glomeruli of the majority of pathological samples. The highest incidence of MMP-11 immunopositivity (26.3%) was noticed in glomerulonephritides associated with microscopic polyangiitis and Wegener's granulomatosis. Generally, MMP-11 was often expressed in segmental areas of sclerosis, microadhesions, cellular and fibrocellular crescents. Fibrotic crescents and fibrotic glomeruli were constantly MMP-11-immunonegative. In MMP-11 immunoreactive glomeruli, increased numbers of macrophages were often detected in the mesangium (P = 0.001), while no such observation could be made with regard to proliferating cells (P = 0.170).

Conclusions. MMP-11, like an inflammatory mediator, may exert a chemotactic influence on macrophages which aggregate in the mesangium; MMP-11 is not likely to have a parallel mitogenic or antifibrotic effect in diseased glomeruli.

Keywords: glomerulonephritis; immunohistochemistry; macrophages; matrix metalloproteinase-11; microscopic polyangiitis.
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