The expression of matrix metalloproteinase-11 protein in various types of glomerulonephritis.
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.
Nakopoulou
Lydia
L
Department of Pathology, The Athens National University Medical School, 75 Mikras Asias str., Goudi, GR-115 27 Athens, Greece. lnakopou@cc.uoa.gr
Lazaris
Andreas C
AC
Boletis
Ioannis
I
Michail
Spyros
S
Iatrou
Christos
C
Papadakis
Gabriel
G
Athanassiadou
Sophia
S
Stathakis
Charalambos
C
D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001706:Biopsy; D049109:Cell Proliferation; D015971:Gene Expression Regulation, Enzymologic; D005921:Glomerulonephritis / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007674:Kidney Diseases / Q000378:metabolism; D008177:Lupus Vulgaris / Q000150:complications*; D008264:Macrophages / Q000378:metabolism; D053507:Matrix Metalloproteinase 11 / Q000096:biosynthesis*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019394:Ki-67 Antigen; D053507:Matrix Metalloproteinase 11; C067980:CD68 antigen, human; D000097382:CD68 Molecule