Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

Cellular proliferation and extracellular matrix accumulation are characteristic features of progressive glomerular diseases in humans, in which the interactions between platelet-derived growth factor (PDGF) and TGF-beta have been consistently implicated. Tranilast (n-[3,4-dimethoxycinnamoyl] anthranilic acid), an anti-fibrotic agent used to treat hypertrophic scars and scleroderma, has been shown to reduce the activation of PDGF and TGF-beta signalling pathways in experimental progressive renal disease. We therefore sought to examine the effects of tranilast on PDGF induced mesangial cell proliferation in vitro, and further to determine whether tranilast ameliorates experimental mesangial proliferation, and matrix accumulation in Thy1 nephritis. In cultured mesangial cells, PDGF (50 ng/ml) induced a 2 to 3 fold increase in mesangial cell 3H-thymidine incorporation. Tranilast (0 to 100 micro-mol/L) reduced PDGF stimulated mesangial cell proliferation in a dose-dependent manner (Table 1). Experimental mesangial proliferative glomerulonephritis was induced in male Wistar rats with monoclonal OX-7, anti-rat Thy-1.1 antibody and rats were randomised to receive either tranilast (400mg/kg/day/gavage) or vehicle. Tranilast was associated with a significant reduction in proteinuria, glomerular hypercellularity, mesangial cell proliferation, the proportional area of activated (alpha-smooth muscle actin positive) mesangial cells, macrophage proliferation, and glomerular type IV collagen deposition (Table 2).The findings of the present study suggest that tranilast is renoprotective in the setting of anti-Thy-1 nephritis. Furthermore, this therapeutic strategy may be beneficial for the treatment of progressive glomerular diseases.