PROGRESSIVE RENAL LESIONS INDUCED BY ADMINISTRATION OF MONOCLONAL-ANTIBODY-1-22-3 TO UNILATERALLY NEPHRECTOMIZED RATS

A new animal model of progressive glomerulosclerosis was developed by administering a single i.v, injection of MoAb 1-22-3 to unilaterally n ephrectomized rats. Renal morphological analysis revealed that glomeru lar lesions characterized by mesangial cell proliferation and mesangia l matrix expansion were induced in about 95% of the glomeruli. Approxi mately 20% of the glomeruli of the unilaterally nephrectomized rats sh owed sclerosis or segmental sclerosis by week 6 after MoAb injection a nd crescent formation was observed in some glomeruli (ca 4%). Cellular infiltration was also noted in some parts of the interstitium. Increa sed expression of transforming growth factor-beta (TGF-beta) was obser ved in the unilaterally nephrectomized rats treated with MoAb 1-22-3, but we could not demonstrate pathological involvement of platelet-deri ved growth factor (PDGF), even though early-stage mesangial cell proli feration was observed. The mechanism of mesangial cell proliferation i n this model remains to be elucidated. The relatively short period of time needed to induce the sclerotic changes is considered to be a grea t advantage of this model for clarifying the mechanisms involved in th e chronic progression of mesangial proliferative glomerulonephritis.