A NOVEL RAT MESANGIAL MATRIX PROTEIN, MMP-50 100, INVOLVED IN MESANGIAL GLOMERULOPATHIES/

BACKGROUND: Within the glomerular extracellular matrix, the glomerular basement membrane and the mesangial matrix have different composition s, presumably related to their different functions. In this study, a n ovel mesangial matrix protein is recognized by mAb ED5 and KiM4R, whic h were originally selected for reactivity with follicular dendritic ce lls 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 o f IMMP-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 w ith mesangial glomerulopathies. RESULTS: Immunoelectron microscopy sho wed 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 glycop rotein with chains of apparent molecular weights of 50 and 100 kDa. Bo th in vivo and in vitro results indicate that MMP-50/100 does not appe ar to be a complement factor, or an Fe 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 chr onic serum sickness nephritis, in rats with anti-Thy-1 nephritis, and in rats with uninephrectomy-induced focal glomerular sclerosis, the me sangial expression of MMP-50/100 was significantly increased In the fi rst model, double-label immunofluorescence demonstrated identical loca lization of MMP-50/100 with mesangial immune complex deposits. CONCLUS IONS: We conclude that MMP-50/100 is an intrinsic component of the mes angial matrix, presumably related to the ''classic'' mesangial cell. E xpression of MMP-50/100 is increased in expanded mesangial matrices du ring development of glomerular disease. Furthermore, MMP-50/100 appear s to be involved in the handling of mesangial immune complexes.