Roles of TGF-beta and latent TGF-beta-binding protein in glomerulosclerosis induced by two consecutive injections of monoclonal antibody 1-22-3 in rats.

Abstract

The present study demonstrated the elevated synthesis and gene expressions of transforming growth factor beta (TGF-beta) or latent TGF-beta binding protein (LTBP) in an irreversible glomerulosclerosis rat model induced by two consecutive injections of monoclonal antibody (MoAb) 1-22-3. The rats were intravenously injected with 500 microg of MoAb 1-22-3 either once or twice at an interval of 2 weeks. The rats were sacrificed at 24 h, 1 week, 2 weeks or 16 weeks after the last injection. At 24 h, the mesangiolytic changes in the rats with two injections of MoAb 1-22-3 were similar to those in the rats with one injection. The glomerular matrix score in the rats with two injections was significantly higher than that in the rats with one injection at weeks 1, 2 or 16. An increased LTBP localization in the glomeruli of the rats at week 1 after either one or two injections was detected in the segmentally expanded mesangial matrix. Moreover, LTBP in the glomeruli of rats at week 1 after two injections appeared to be more strongly stained in the enlarged mesangial matrix than that in the rats after one injection. A TGF-beta bioassay using mink lung epithelial cells revealed that the total TGF-beta in the glomerular culture conditioned medium in the rats at week 1 after two injections was significantly larger than that in the rats after one injection. A Northern blotting analysis of the glomeruli showed that both the expressions of TGF-beta and LTBP mRNA in the rats after two injections were higher than those in the rats after one injection. These findings suggested that the elevated TGF-beta or LTBP may thus be related to the irreversible glomerulosclerosis that was induced by two injections of MoAb 1-22-3 into rats.