NDT Advance Access originally published online on November 3, 2006
Nephrology Dialysis Transplantation 2007 22(1):109-117; doi:10.1093/ndt/gfl618
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The expression of matrix metalloproteinase-11 protein in various types of glomerulonephritis
12nd Department of Pathology, "Attikon" University Hospital, School of Medicine, The National and Kapodistrian University of Athens, 2Department of Nephrology, "Laikon" General Hospital of Athens, 3Department of Nephrology, General Regional Hospital of Nikea, Piraeus and 4Department of Nephrology, "Tzanio" Regional General Hospital of Piraeus, Greece
Correspondence and offprint requests to: Prof. Dr Lydia Nakopoulou, Department of Pathology, The Athens National University Medical School, 75 Mikras Asias str., Goudi, GR-115 27 Athens, Greece. Email: lnakopou{at}cc.uoa.gr; alazaris{at}med.uoa.gr
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Abstract |
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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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