title: Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis.
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 new, highly effective therapeutic approach to progressive, in particular mesangioproliferative, renal disease.
authors.affiliation: Medizinische Klinik II, University of Aachen, Aachen, Germany.
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
authors.affiliation: Medizinische Klinik II, University of Aachen, Aachen, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Kunter
authors.affiliation: Department of Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Hermann Joseph
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Division of Nephrology, Medizinische Hochschule, Hannover, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Bahlmann
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata School of Medicine, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata School of Medicine, Niigata, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Shimizu
authors.affiliation: Division of Nephrology, Medizinische Hochschule, Hannover, Germany.
authors.forename: Karl Martin
authors.initials: KM
authors.lastname: Koch
authors.affiliation: NeXstar Pharmaceuticals, Boulder, Colorado.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Janjic
authors.affiliation: Medizinische Klinik II, University of Aachen, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002921:Cicatrix / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D011507:Proteinuria / Q000517:prevention & control; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D003094:Collagen