Gene therapy for progressive renal diseases

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11694275
• Research Category: Grant-in-Aid for Scientific Research (B).
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: ENYU Imai Osaka University Graduate School of Medicine, Lecture, 医学系研究科, 講師 (00223305)
• Co-Investigator(Kenkyū-buntansha): TAKENAKA Masaru Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20222101)
• Project Period (FY): 1999 – 2000
• Keywords: glomerulonephritis / gene therapy / HVJ-liposome / interleukin 10

Research Abstract

Inflammatory processes within the glomerulus are switched off by the local generation of anti-inflammatory mediators. These mediators include eicosanoids (e.g., lipoxins), anti-inflammatory cytokines (interleukins 4 and 13), antagonists of proinflammatory cytokines (interleukin 1 receptor antagonist), neuropoietic cytokines (leukemia inhibitory factor and interleukin 6), as well as deactivators of inflammatory macrophages (transforming growth factor beta and interleukin 10). They limit the effects of proinflammatory mediators by inhibiting their production, stability, or function. Recent attempts to reduce inflammatory lesions in experimental glomerulonephritis have focused on upregulating the expression of these anti-inflammatory mediators by using protein or gene transfer. In particular administration of interleukin 4, interleukin 1 receptor antagonist, leukemia inhibitory factor, or interleukin 10 has been shown to be effective in the treatment of nephrotoxic nephritis. Of all the mediators already tested, interleukin 10 has the greatest potential because of its strong anti-inflammatory effects and weak adverse effects.

Research Products

• [Publications] Baud L,Fouqueray B,Bellocq A: "Cytokines and hormones with anti-inflammatory effects : new tools for therapeutic intervention"Curr Opin Nephrol Hypertens. 10. 49-54 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Isaka,Y, et al: "Transforming growth factor-β1 antisense oligodeoxynucleotides block intersutitial fibrosis in unilaterall ureteral obstruction."Kidney Int.. 58. 1885-1892 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Isaka,Y, et al: "Gene transfer targeting interstitial. Fibroblasts by the artificial viral envelope type hemagglutinating virus of Japan liposome method."Kidney Int.. 57. 1973-1980 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Isaka,Y, et al: "Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular ntatrix accumulation in experimental glomerulonephritis"Kidney Int.. 55. 465-475 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Baud L, Fouqueray Bellocq A: "Cytokines and hormones with anti-inflammatory effects : new tools for therapeutic intervention"Curr Opin Nephrol Hypertens. 10. 49-54 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Isaka Y, Tsujie M, Ando Y, Nakamura H, Kanada Y, Imai E, Horio M: "Transforming growth factor-β1 antisense oligodeoxynucleotides block intersutitial fibrosis in unilateral ureteral obstruction"Kidney Int. 58. 1885-1892 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsujie M, Isaka Y, Ando Y, Akagi Y, Kaneda Y, Ueda N, Imai E, Hori M.: "Gene transfer targeting interstitial fibroblasts by the artificial viral envelope type hemagglutinating virus of Japan liposome method."Kidney Int. 57. 1973-1980 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Isaka Y, Akagi Y, Ando Y, Tsujie M, Sudo T, Ohno N, Border WA, Noble NA, Kaneda Y, Hori M, Imai E: "Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular matrix accumulation in experimental glomerulonephritis."Kidney Int. 55. 465-475 (1999)
  • Description: 「研究成果報告書概要(欧文)」より