IDENTIFICATION OF GENES SPECIFICALLY EXPRESSED IN CHRONIC AND PROGRESSIVE GLOMERULOSCLEROSIS

To identify genes expressed predominantly in the kidney with chronic a nd progressive glomerulosclerosis but not in acute and transient form of glomerulonephritis, we induced progressive glomerulosclerosis in ra ts by applying unilateral nephrectomy prior to injection of monoclonal anti-Thy1.1 antibody (OX-7), which cause acute and transient glomerul onephritis with single injection. In rats with nephrectomy and OX-7 in jection (Nx group), proteinuria increased with time and mesangial expa nsion accompanied with interstitial fibrosis was recognized, whereas t ransient proteinuria and mesangiolysis followed by mesangial hypercell ularity were seen in rats with sham operation and OX-7 injection (Sham group). Four weeks after the induction of glomerulonephritis, mRNAs w ere isolated from kidney cortex of both groups and used for cDNA synth esis. By subtraction hybridization of cDNAs from Nx with excess amount of those from Sham, we isolated and sequenced several genes expressed specifically in the Nx group. These included genes, which contain ide ntical sequences with serine protease inhibitors, cytokine receptors, osteopontin as well as genes with unknown function. These genes may pl ay important roles in the process which promotes acute glomerular dama ge advance to chronic and progressive glomerulosclerosis.