A novel rat mesangial matrix protein, MMP-50/100, involved in mesangial glomerulopathies

Abstract

Background: Within the glomerular extracellular matrix, the glomerular basement membrane and the mesangial matrix have different compositions, presumably related to their different functions. In this study, a novel mesangial matrix protein is recognized by mAb ED5 and KiM4R, which were originally selected for reactivity with follicular dendritic cells of rat lymphoid organs.

Experimental design: Distribution of this mesangial matrix protein (MMP-50/100) was studied in normal Wistar rat kidneys by indirect immunofluorescence and immunoelectron microscopy. For partial immunobiochemical characterization, ED5-affinity-purified glomerular matrices were subjected to SDS-PAGE analysis. Expression of MMP-50/100 was additionally studied in kidneys of rats depleted for complement and in kidneys of rats depleted for resident macrophages. Functional significance of MMP-50/100 was studied in kidneys of rats with mesangial glomerulopathies.

Results: Immunoelectron microscopy showed that MMP-50/100 is located in the extracellular matrix of the rat renal mesangium between mesangial cells and the basement membrane and on the mesangial cell membrane. SDS-PAGE analysis of affinity-purified glomerular matrices indicated that MMP-50/100 is a polypeptide glycoprotein with chains of apparent molecular weights of 50 and 100 kDa. Both in vivo and in vitro results indicate that MMP-50/100 does not appear to be a complement factor, or an Fc or complement receptor. In rats partially depleted for resident macrophages, the expression of MMP-50/100 was similar to that in control rats. In rats with BSA-induced chronic serum sickness nephritis, in rats with anti-Thy-1 nephritis, and in rats with uninephrectomy-induced focal glomerular sclerosis, the mesangial expression of MMP-50/100 was significantly increased. In the first model, double-label immunofluorescence demonstrated identical localization of MMP-50/100 with mesangial immune complex deposits.

Conclusions: We conclude that MMP-50/100 is an intrinsic component of the mesangial matrix, presumably related to the "classic" mesangial cell. Expression of MMP-50/100 is increased in expanded mesangial matrices during development of glomerular disease. Furthermore, MMP-50/100 appears to be involved in the handling of mesangial immune complexes.