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)-beta1 production in accelerated
IgA nephropathy, kidneys were isolated and measured
TGF-beta1 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-beta1 in glomeruli of accelerated
IgA nephropathy. Treatment with
TJN-259 inhibited the increases in renal total and mature
TGF-beta1 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-beta1 production in glomeruli.