| الوصف: |
In order to elucidate the molecular mechanisms, in which acute and basically selflimited glomerular injury advance to chronic and progressive glomerulosclerosis, we tried to identify genes expressed predominantly in the kidney of chronic and progressive glomerulosclerosis but less in acute and transient glomerulonephritis. Progressive glomerulosclerosis was induced in male Sprague－Dawley rats by unilateral nephrectomy followed by monoclonal anti-Thy1. 1 antibody （OX－7） injection （Nx）. Control rats were sham operated and injected with OX’7 （Sham） to induce acute and transient glomerulonephritis. Urinary protein measurement and morphological examinations were performed until 6 months after the disease induction. In Nx rats, proteinuria increased with time and mesangial expansion was accompanied by interstitial fibrosis, whereas, in Sham rats, transient proteinuria peaked at 1 week and mesangiolysis was followed by mesangial hypercellularity which was dissolved spontaneously after 4 weeks. Four weeks after the induction of the chronic （Nx） and acute（Sham）glomerulonephritis, before any remarkable histological difference between both groups was evident, mRNAs were isolated from kidney cortex of the groups and used for cDNA synthesis. By subtraction hybridization of cDNAs from Nx with an excess amount of those from Sham, We isolated and characterized several genes expressed predominantly in the Nx group. These included genes that encode serine protease inhibitors, ligands for cytokines, osteopontin, and those for de novo protein synthesis as well as those with unknown function. Osteopontin expression was immunohistologically found to be upregulated in Nx at 4 weeks after the disease induction, whereas no remarkable expression was found in the Sham group. In conclusion, we have identified genes expressed predominantly in chronic glomerulosclerosis but less in acute glomerulonephritis. These genes may play important roles in the process which promotes initial glomerular injury to result in chronic and progressive glomerulosclerosis. |
