Abstract
Meprin (EC 3.4.24.18) is an oligomeric metalloendopeptidase found in microvillar membranes of kidney proximal tubular epithelial cells. Here, we present the first report on the expression of meprinβ in rat glomerular epithelial cells and suggest a potential involvement in experimental glomerular disease. We detected meprinβ in glomeruli of immunostained rat kidney sections on the protein level and by quantitative RT-PCR of laser-capture microdissected glomeruli on the mRNA level. Using immuno-gold staining we identified the membrane of podocyte foot processes as the main site of meprinβ expression. The glomerular meprinβ expression pattern was altered in anti-Thy 1.1 and passive Heymann nephritis (PHN). In addition, the meprinβ staining pattern in the latter was reminiscent of immunostaining with the sheep anti-Fx1A antiserum, commonly used in PHN induction. Using Western blot and immunoprecipitation assays we demonstrated that meprinβ is recognized by Fx1A antiserum and may therefore represent an auto-antigen in PHN. In anti-Thy 1.1 glomerulonephritis we observed a striking redistribution of meprinβ in tubular epithelial cells from the apical to the basolateral side and the cytosol. This might point to an involvement of meprinβ in this form of glomerulonephritis.
Highlights
Many forms of inflammatory kidney disease are characterized by excessive proliferation of mesangial cells (MC) and by increased deposition of extracellular matrix (ECM) in glomeruli and the tubulo-interstitium, with subsequent structural alteration of the glomerular basement membrane (GBM) and the mesangial matrix [1,2]
We focused on meprinb expression in healthy rat kidney and in two models of rat glomerular disease: passive Heymann nephritis (PHN), a rat model of human membranous nephropathy, and anti-Thy 1.1 mesangial proliferative nephritis [3,40,41,42]
In our study we detected for the first time meprinb expression in the glomeruli of three different rat strains, a finding expanding our knowledge on meprin’s previously described expression in the apical membrane of proximal tubular epithelial cells
Summary
Many forms of inflammatory kidney disease are characterized by excessive proliferation of mesangial cells (MC) and by increased deposition of extracellular matrix (ECM) in glomeruli and the tubulo-interstitium, with subsequent structural alteration of the glomerular basement membrane (GBM) and the mesangial matrix [1,2]. Meprin (EC 3.4.24.18), an oligomeric zinc endopeptidase of the astacin family, was originally identified on the apical brush-border membrane of epithelial cells in the corticomedullary portion of proximal kidney tubules and the intestine [12,13,14,15]. It is composed of a and b subunits that are expressed separately or coordinately either forming homo- or heterooligomeric complexes [16,17]. Meprins act extracellularly in that they are either bound to the plasma membrane by transmembrane domains or secreted into the extracellular space [28,29]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
