Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis

Glomerular mesangial cell proliferation and/or mesangial matrix accumulatio n characterizes many progressive renal diseases. Rats with progressive mesa ngioproliferative glomerulonephritis were treated from day 3 to day 7 after disease induction with a high-affinity oligonucleotide aptamer-antagonist against platelet-derived growth factor-B chain (PDGF-B), In comparison with nephritic rats that received vehicle or a scrambled aptamer, treatment wit h the PDGF-B aptamer led to a significant reduction of mesangioproliferativ e changes, glomerular hypertrophy, podocyte damage, and glomerular macropha ge influx on day 8. Both nephritic control groups subsequently developed pr ogressive proteinuria and decreased renal function. On day 100, glomerulosl erosis, tubulointerstitial damage, glomerular and interstitial accumulation of types III and IV collagen, and overexpression of transforming growth fa ctor-beta were widespread. All of these chronic changes were prevented in r ats that received the PDGF-B aptamer, and their functional and morphologic parameters on day 100 were largely indistinguishable from non-nephritic rat s. These data provide the first evidence for a causal role of PDGF in the p athogenesis of renal scarring and point to a new, highly effective therapeu tic approach to progressive, in particular mesangioproliferative, renal dis ease.