Analysis of glomerulosclerotic mechanism by monoclonal antibody-induced progressive renal lesion model in rats

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I rreversible sclerotic renal lesions were induced in rats by an intravenous injection of 500 ug of anti-Thy-1.1 monoclonal antibody (mAb) 1-22-3to unilaterally nephrectomized rats. This modelis characterized by the sustained marked proteinuria with typical sclerotic lesions in glomeruli as well as in tubulointerstitium. These lesions were inhibited by adhesive molecules suppressants, complement inhibitors, anti-fibrotic agents, ACE inhibitors and Chinese traditional medicines. We have compared the kinetics of various parametersofirreversible to those in reversiblemodels, both of which were induced by an intravenous injection of mAb 1-22-3. In irreversible models TRPM3-positive activated macrophage and alpha -smoothe muscle actin-positive cells were demonstrated to infiltrate to interstitium, even in relatively early phase, suggesting the important roles playd by these tubulointerstitiallesionsin leading to irreversiblescleroticlesions. Angiotensin receptorantagonist prevented progression to endo-stage renal failure by suppressing the expression of TGF-beta and type I,III collagens at mRNA and protein levels, indicating that these factors are also important for irreversible progression of renal lesions.