Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis.

Journal of the American Society of Nephrology : JASN
T OstendorfJ Floege

Abstract

Glomerular mesangial cell proliferation and/or mesangial matrix accumulation characterizes many progressive renal diseases. Rats with progressive mesangioproliferative 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 with the PDGF-B aptamer led to a significant reduction of mesangioproliferative changes, glomerular hypertrophy, podocyte damage, and glomerular macrophage influx on day 8. Both nephritic control groups subsequently developed progressive proteinuria and decreased renal function. On day 100, glomerulosclerosis, tubulointerstitial damage, glomerular and interstitial accumulation of types III and IV collagen, and overexpression of transforming growth factor-beta were widespread. All of these chronic changes were prevented in rats that received the PDGF-B aptamer, and their functional and morphologic parameters on day 100 were largely indistinguishable from non-nephritic rats. These data provide the first evidence for a causal role of PDGF in the pathogenesis of renal scarring and point to a n...Continue Reading

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Citations

Jun 24, 2003·Journal of the American Society of Nephrology : JASN·Wilhelm KrizJürgen Floege
Aug 26, 2003·Journal of the American Society of Nephrology : JASN·Tammo OstendorfJürgen Floege
Apr 4, 2007·The Journal of Biological Chemistry·Derick MitchellCatherine Godson
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Apr 17, 2003·Current Opinion in Nephrology and Hypertension·Frank Eitner, Jürgen Floege
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Aug 12, 2005·Journal of the American Society of Nephrology : JASN·Claudia R C van RoeyenPeter R Mertens
Mar 3, 2006·Journal of the American Society of Nephrology : JASN·Tammo OstendorfJürgen Floege
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Dec 14, 2007·Journal of the American Society of Nephrology : JASN·Jürgen FloegeCharles E Alpers
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