ROLES OF TGF-BETA AND LATENT TGF-BETA-BINDING PROTEIN IN GLOMERULOSCLEROSIS INDUCED BY 2 CONSECUTIVE INJECTIONS OF MONOCLONAL-ANTIBODY 1-22-3 IN RATS

The present study demonstrated the elevated synthesis and gene express ions 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 mu g of MoAb 1-22 -3 either once or twice at an interval of 2 weeks, The rats were sacri ficed at 24 h, 1 week, 2 weeks or 16 weeks after the last injection, A t 24 h, the mesangiolytic changes in the rats with two injections of M oAb 1-22-3 were similar to those in the rats with one injection, The g lomerular matrix score in the rats with two injections was significant ly 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 e xpanded mesangial matrix. Moreover, LTBP in the glomeruli of rats at w eek 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 ra ts at week 1 after two injections was significantly larger than that i n the rats after one injection, A Northern blotting analysis of the gl omeruli 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.