PDGF signal transduction inhibition ameliorates experimental mesangial proliferative glomerulonephritis

Abstract

Background. Platelet-derived growth factor (PDGF) has been consistently implicated in the cell proliferation and extra-cellular matrix accumulation, which characterize progressive glomerular disease. In the present study, the effects of a potent and selective inhibitor of PDGF receptor tyrosine kinase, STI 571, were examined in vitro and in vivo. Methods. Cultured mesangial cells were incubated with PDGF (50 ng/mL) and fibroblast growth factor-2 (FGF-2; 50 ng/mL) and treated with STI 571 (0.13 to 2.0 μmol/L). Experimental mesangial proliferative glomerulonephritis was induced in male Wistar rats with monoclonal OX-7, anti-rat Thy-1.1 anti-body with rats randomized to receive either STI 571 (..