TJN-259 Improves Mesangial Lesions in Experimental Immunoglobulin A Nephropathy in ddY Mice

摘要

TJN-259 is a chemical substance based on the structural features of the botanically derived ingredient acteoside. This study was performed in order to elucidate the antinephritic effects of TJN-259 in experimental immunoglobulin A (IgA) nephropathy. In this study, 28-week-old ddY mice were used as a spontaneous model of IgA nephropathy. With regard to spontaneous IgA nephropathy, we investigated the effects of TJN-259 administered from 28 to 40 weeks. In addition, an accelerated model of IgA nephropathy was experimentally induced in ddY mice by oral administration of bovine serum albumin, followed by reticuloendothelial blocking by colloidal carbon injection and heminephrectomy. At 10 weeks after the 3rd carbon injection, we also examined the effects of TJN-259 on accelerated IgA nephropathy. To investigate the effects of TJN-259 on transforming growth factor (TGF)-beta 1 production in accelerated IgA nephropathy, kidneys were isolated and measured TGF-beta 1 by the enzyme-linked immunosorbent assay (ELISA) method. The administration of TJN-259 to mice with spontaneous IgA nephropathy decreased the incidence of mesangial expansion as well as the number of nuclei per glomerular cross-section in comparison with that of non-treated mice. In addition, TJN-259 treatment prevented the increase in the incidence of mesangial expansion, crescent formation, and segmental sclerosis in glomeruli in accelerated IgA nephropathy. TJN-259 also inhibited the increased immunostaining score of collagen type IV and TGF-beta 1 in glomeruli of accelerated IgA nephropathy. Treatment with TJN-259 inhibited the increases in renal total and mature TGF-beta 1 protein levels in accelerated type IgA nephropathy. TJN-259 failed to inhibit the increase in serum IgA levels in both models. These results suggest that TJN-259 was an effective treatment against IgA nephropathy in ddY mice, acting via the suppression of TGF-beta 1 production in glomeruli.