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.

Evaluation of E-cadherin/catenin complex in primary and secondary glomerulonephritis.

Catenins (alpha-, beta-, gamma-catenin, p120(ctn)) are cytoplasmic proteins initially identified in a complex with E-cadherin (ECD). The latter belongs to a superfamily of transmembrane glycoproteins important for cell adhesion in normal and disease states. Catenins and p120(ctn), in particular, are substrates for growth factor receptor tyrosine kinases. Cell adhesive mechanisms have an impact on cell migration and proliferation and thus are potentially involved in the pathogenesis of glomerulonephritides (GNs). Using appropriate monoclonal antibodies, we investigated the immunohistochemical expression of ECD, alpha-catenin, beta-catenin, gamma-catenin, and p120(ctn) in renal biopsy specimens from 95 patients with primary GN (n = 51) and secondary lupus-associated GN (n = 44). Examined cases were divided into two groups (proliferative [n = 35] and nonproliferative [n = 60] GNs). Among examined molecules, p120(ctn), beta-catenin, and gamma-catenin were expressed more frequently in glomerular epithelial cells, mainly in parietal epithelium (76%, 48%, and 40%, respectively). p120(ctn) and gamma-catenin epithelial expression appeared to be linked closely with proliferative lupus-associated GNs (P = 0.050 and P = 0.029, respectively). Mainly in lupus GNs, with regard to cellular crescents and epithelial cells around microadhesions to Bowman's capsule, p120(ctn) (63% and 73%, respectively), beta-catenin (72% and 75%), and gamma-catenin (75% and 64%) showed the greatest frequencies of positive detection. Mesangial cells were positive only occasionally for the examined molecules. In proliferative lupus GNs, expression of beta-catenin in mesangial cells tended to be prominent (P = 0.066). ECD and alpha-catenin were not expressed in cellular crescents or microadhesions, whereas only ECD was barely detectable in glomerular epithelial cells. In conclusion, expression of beta-catenin, gamma-catenin, and p120(ctn) is focused on glomerular epithelium, as well as on such lesions deriving from it as cellular crescents. This expression probably is linked with epithelial cells' responses to various mitogens, such as growth factors.