Metalloprotease Meprinβ in Rat Kidney: Glomerular Localization and Differential Expression in Glomerulonephritis

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.

Specific processing of tenascin-C by the metalloprotease meprinβ neutralizes its inhibition of cell spreading

“…However, under certain pathological conditions they also appear basolaterally. This was shown for meprinα in human colon carcinoma cells (Lottaz et al, 1999b) and in the kidney of rodents with renal disease (Walker et al, 1998;Oneda et al, 2008). Furthermore, both meprin subunits, α and β, are expressed by leukocytes of the lamina propria (Lottaz et al, 1999a).…”

Metalloprotease Meprin β Generates Nontoxic N-terminal Amyloid Precursor Protein Fragments in Vivo

“…RNA was extracted from 10 human brain samples and analyzed for meprin ␤ expression. The data were normalized and compared with the expression of meprin ␤ in the kidney, a tissue that is known to highly express the enzyme (46,47). Interestingly, the expression level of meprin ␤ in the brains analyzed here was on average 21.6 times higher compared with the level of meprin ␤ detected in the kidney RNA sample (Fig.…”

“…Three different RNA samples were used as reference for the normalized transcript levels of meprin (see "Experimental Procedures"). Adult human renal total RNA was used as reference because expression of meprin ␤ in mouse and human kidney has been reported previously (46,47). Expression levels in the brains analyzed were compared with the level of meprin detected in the kidney RNA sample (data were obtained from duplicates of four independent experiments).…”

ADAM10 Is the Major Sheddase Responsible for the Release of Membrane-associated Meprin A

“…Expression of meprins has also been identified in human skin epithelia (2), leukocytes in the lamina propria of the human inflamed bowel (3,4), mesenteric lymph nodes (5), colorectal (3,4) and breast cancer cells (6), and recently in glomeruli of some strains of rat (7). Meprins are oligomeric neutral metalloproteinases composed of two evolutionarily related subunits, ␣ and ␤, that form homo-or hetero-oligomeric structures (1,8,9).…”