Increased expression of cytoplasmic tail-containing form of gp600/megalin in active Heymann nephritis

Active Heymann nephritis of rat, an autoimmune glomerular disease, is a model of human membranous glomerulonephropathy. The major target autoantigen of this disease is a 600 kD renal glycoprotein, variously named gp600/gp330/megalin/LRP2. It has been shown previously that there is a marked increase in the gp600/megalin mRNA level in glomeruli of rats with this disease. A rabbit antibody was prepared against a peptide located at the very end of the cytoplasmic tail of rat gp600/megalin. Affinity purified anti-peptide antibody was monospecific and reacted only with gp600/megalin on the immunoblots of total kidney proteins. Immunofluorescence microscopy on frozen kidney sections probed with this antibody revealed the presence of the cytoplasmic tail-containing form of gp600/megalin in both proximal tubules and glomeruli. Expression in glomeruli of normal kidneys was less than in tubules but was clearly detectable. In active Heymann nephritis kidneys, expression of this form was increased most remarkably in glomeruli. These results, showing increased expression of the cytoplasmic tail-containing form in active Heymann nephritis glomeruli, contradict previous reports of its absence. This is the first study to show that there is increased expression of the cytoplasmic tail-containing form of gp600/megalin in the glomeruli of rats with this disease and its role in active Heymann nephritis is discussed.