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2001 Fiscal Year Final Research Report Summary

Application of anti-adhesion molecule therapy for glomerulonephritis -Effects of sulfated oligosaccharides as selectin-blocking agents-

Research Project

Project/Area Number 11671036
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionOkayama University

Principal Investigator

SHIKATA Kenichi  Okayama University, Hospital, Lecturer, 医学部・附属病院, 講師 (00243452)

Co-Investigator(Kenkyū-buntansha) HIDA Kazuyuki  Okayama University, Hospital, Senior Resident, 医学部・附属病院, 医員
WADA Jun  Okayama University, Graduate School of Medicine and Dentistry, Assistant, 大学院・医歯学総合研究科, 助手 (30294408)
Project Period (FY) 1999 – 2000
Keywordsglomerulonephritis / macrophage / adhesion molecule / selectin / hyaluronic acid / colominic acid / iNOS / therapy
Research Abstract

Background. Selectins are adhesion molecules which mediate leukocyte infiltration into inflammatory tissues. P- and L-selectin bind to sulfated oligosaccharide chains on the ligand molecules. Synthesized sulfated oligosaccharides, including sulfated hyarulonic acid (SHA) and sulfated colominic acid (SCA), inhibit both P- and L-selectin-dependent adhesion pathways in vitro. We evaluated the preventive effects of SHA and SCA on rat mesangial proliferative glomerulonephritis and rat crescentic glomerulonephritis.
Methods. Female Wistar rats were injected with anti-Thy-1 antibody after unilateral nephrectomy for a mesangial proliferative glomerulonephritis model. Female WKY rats were injected with nephrotoxic serum for a crescentic glomerulonephritis model. Rats were administered with neutralizing or non-neutralizing monoclonal antibodies to rat P-selectin and L-selectin, SHA, hyarulonic acid, SCA and colominic acid. Localization of P-selectin and macrophages were examined by immunohistochemical methods. Gene expression of PDGF B chain in the glomeruli was quantified using real-time RT-PCR method.
Results. Increased expression of P-selectin and macrophage infiltration was prominent in the glomeruli in both two models. Proteinuria, crescent formation and glomerular infiltration of macrophages were significantly reduced by anti-P-selectin mAb, but not by anti-L-SL mAb. SHA and SCA reduced proteinuria, macrophage infiltration and crescent formation in dose dependent manner. Gene expression of PDGF B chain was significantly decreased in SHA and SCA treatment groups. In conclusion, SHA and SCA inhibited glomerular macrophage infiltration by blocking P-selectin-dependent adhesion pathway, and prevented disease progression in rat mesangial proliferative glomerulonephritris and rat crescentic glomerulonephritis. We conclude that sulfated oligosaccharides may be beneficial for the treatment of glomerulonephritis.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Ogawa S et al.: "Preventive effect of sulfated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally-induced crescentic glomerulonephritis"Clincal Experimental Immunology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikata K.et al.: "Role of macrophages in the pathogenesis of diabetic nephropathy"Contributions to Nephrology. 134. 46-54 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada J, et al.: "Gene expression profile in strepotozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis"Kidney International. 59. 1363-1373 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuchiyama Y. et al.: "Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats"Kidney International. 58. 1941-1952 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 四方賢一, 他: "腎臓病と接着分子"現代医療,32:59-67,2000. 32. 59-67 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 四方賢一, 他: "糖尿病と腎症-その新しい展開-発症・進展機構-浸潤マクロファージ"Diabetes Frontier. 11. 677-684 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa S, Shikata K, Matsuda M, Okada S, Wada J, Yamaguchi S, Suzuki Y, Miyasaka M, Tojo S, Makino H: "Preventive effect of sulfated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally-induced crescentic glomerulonephritis."Clincal Experimental Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikata K, Makino H: "Role of macrophages in the pathogenesis of diabetic nephropathy."Contributions to nephrology. 134. 46-54 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada J, Zhang H, Tsuchiyama Y, Hiragushi K, Hida K, Shikata K, Kanwar YS, Makino H: "Gene expression profile in strepotozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis."Kidney International. 59 (4). 1363-1373 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuchiyama Y, Wada J, Zhang H, Morita Y, Hiragushi K, Hida K, Shikata K, Yamamura M, Kanwar YS, Makino H: "Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats."Kidney International. 58. 1941-1952 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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