Transforming growth factor-b1 (TGF-b1) induces matrix synthesis in renal tissues, leading to the progression of IgA nephropathy. When added to cultured human mesangial cells, aggregated IgA1 from patients with IgA nephropathy induces increases in TGF-b1 gene expression and secretion

lar pathological finding in renal diseases, and it is observed in most proliferative nephritises (including immunoglobulin A (IgA) nephropathy). The mechanism of action of the expansion of the glomerular mesangial region, a particularly notable feature of IgA nephropathy, is not well elucidated, but it is presumed that the inflammatory reactions after deposition of IgA play a critical role. Spontaneous nephropathy models employing HIGA or ddY mice are used as experimental animal models of IgA nephropathy. Analyses of the effects of chemical compounds against IgA nephropathy have been conducted using these models; however, such analyses face an inherent difficulty in identifying the dramatic changes that occur in the inflammatory process because it takes a long time for the models to develop the disease. Until the present time, there have thus been no revolutionary therapeutic agents against IgA nephropathy. On the other hand, unilateral nephrectomy, blockade of the reticuloendothelial system, and oral sensitization in ddY mice have demonstrated that the deposition of IgA and pathological changes in glomeruli may be induced earlier than those in spontaneous ddY mice. Transforming growth factor-b1 (TGF-b1) induces matrix synthesis in renal tissues, leading to the progression of IgA nephropathy. When added to cultured human mesangial cells, aggregated IgA1 from patients with IgA nephropathy induces increases in TGF-b1 gene expression and secretion of extracellular matrix in cultured mesangial cells. These findings suggest that TGF-b1 is a therapeutic target for human IgA nephropathy. Acteoside, which is found in Stachys sieboldii MIQ., dramatically improves urinary protein excretion and histopathological changes in rat anti-glomerular basement membrane (GBM) nephritis and also inhibits mesangial cell expansion in anti-Thy1 nephritis. Acteoside is an herbal drug component that has a structure composed of caffeic acid and phenethyl alcohol bridged by two types of sugar moieties. By screening a series of compounds with pyridyl acrylic amide backbones that were chemically derived from caffeic acid and phenethyl alcohol for potency of antinephritic action in an in vivo assay, a new compound known as TJN-259 was generated. However, the detailed mechanisms of its action have not yet been elucidated. In this study, we investigated the therapeutic effects of TJN-259 on early glomerular lesions in a spontaneous model of IgA deposition and an accelerated model of IgA nephropathy in ddY mice in order to elucidate the effects of TJN-259 on IgA nephropathy.