論文 - 詳細
| RRC ID | 116 |
|---|---|
| 著者 | Takeda S, Takahashi M, Sado Y, Takeuchi K, Hakamata Y, Shimizu H, Kaneko T, Yamamoto H, Ito C, Ookawara S, Asano Y, Kusano E, Kobayashi E. |
| タイトル | Prevention of glomerular crescent formation in glomerulonephritis by mycophenolate mofetil in rats. |
| ジャーナル | Nephrol Dial Transplant |
| 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. |
| 巻・号 | 19(9) |
| ページ | 2228-36 |
| 公開日 | 2004-9-1 |
| DOI | 10.1093/ndt/gfh302 |
| PII | gfh302 |
| PMID | 15238626 |
| MeSH | Animals Anti-Glomerular Basement Membrane Disease / drug therapy Anti-Glomerular Basement Membrane Disease / immunology Anti-Glomerular Basement Membrane Disease / pathology* Female Immunosuppressive Agents / pharmacology* Kidney Glomerulus / drug effects* Kidney Glomerulus / immunology Kidney Glomerulus / pathology Macrophages / drug effects Macrophages / immunology Mycophenolic Acid / analogs & derivatives* Mycophenolic Acid / pharmacology* Osteopontin Proteinuria / drug therapy Rats Rats, Inbred WKY Sialoglycoproteins / biosynthesis Sialoglycoproteins / drug effects T-Lymphocytes / drug effects T-Lymphocytes / immunology |
| IF | 4.531 |
| 引用数 | 16 |
| WOS 分野 | TRANSPLANTATION UROLOGY & NEPHROLOGY |
| リソース情報 | |
| ラット | WKY/NCrlCrlj(strainID=477) |