title: Prevention of glomerular crescent formation in glomerulonephritis by mycophenolate mofetil in rats.
abstract: BACKGROUND
  Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis (GN) and is associated with a poor prognosis. We investigated whether the potent immunosuppressive agent mycophenolate mofetil (MMF) could prevent crescent formation in a model of anti-glomerular basement membrane (GBM) GN in the rat.
  
  
  METHODS
  GN with glomerular crescents was induced by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The experimental rats were divided into two groups: rats received vehicle (0.5% carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and the urine and blood samples were evaluated. The rats were sacrificed at day 14, and histological analysis was performed. The mRNA expression of cytokines and adhesion molecules in the kidney was analysed by reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Marked proteinuria, glomerular crescent formation and glomerulosclerosis were observed in this model, and these were significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell infiltration was also observed, and MMF treatment significantly inhibited macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis revealed that mRNA and protein expression of osteopontin was decreased by the treatment with MMF. In addition, MMF treatment in the early stages of GN could inhibit proteinuria, glomerular crescent formation and glomerulosclerosis.
  
  
  CONCLUSIONS
  These findings suggest therapeutic potential for MMF in the inhibition of glomerular crescent formation in GN and provide new insights into the mechanism underlying the amelioration of crescentic GN by MMF treatment.
authors.affiliation: Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Minamikawachi-machi, Tochigi 329-0498, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hakamata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ito
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ookawara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Asano
authors.forename: Eiji
authors.initials: E
authors.lastname: Kusano
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D053495:Osteopontin; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011921:Rats, Inbred WKY; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D009173:Mycophenolic Acid