Significant Roles of Inducible Cyclooxygenase (COX)-2 in Angiogenesis in Rat Sponge Implants.

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  • Majima Masataka
    Department of Pharmacology, Kitasato University School of Medicine
  • Isono Masako
    Department of Pharmacology, Kitasato University School of Medicine
  • Ikeda Yasuhiro
    Department of Pharmacology, Kitasato University School of Medicine
  • Hayashi Izumi
    Department of Pharmacology, Kitasato University School of Medicine
  • Hatanaka Ko
    Department of Pharmacology, Kitasato University School of Medicine
  • Harada Yoshiteru
    Department of Pharmacology, Kitasato University School of Medicine
  • Katsumata Osamu
    Department of Anatomy, Kitasato University School of Medicine
  • Yamashina Shohei
    Department of Anatomy, Kitasato University School of Medicine
  • Katori Makoto
    Department of Pharmacology, Kitasato University School of Medicine
  • Yamamoto Shozo
    Department of Biochemistry, Tokushima University School of Medicine

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  • Significant Roles of Inducible Cyclooxy

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Abstract

Angiogenesis in rat sponge implants, as determined from the concentration of hemoglobin in the sponge granuloma tissues, was gradually increased over a 14-day experimental period. The inducible cyclooxygenase COX-2 was detected in the sponge granuloma tissues at day 4 by Western blot analysis using specific mouse COX-2 antibody. Angiogenesis in the sponge implants was enhanced by daily topical injections of human recombinant basic fibroblast growth factor (bFGF) or human recombinant epidermal growth factor (EGF) (100 or 1000 ng/sponge/day) for 4 days. These treatments clearly enhanced the expression of COX-2 in the sponge granuloma tissues. In immunohistochemical studies, COX-2-positive staining was mainly observed in the endothelial cells of the neovasculature and in the fibroblasts of the granuloma capsule. Administration of the selective COX-2 inhibitor NS-398 (p.o., 3 mg/kg, 3 times a day) for 14 days significantly inhibited the angiogenesis. The angiogenesis enhanced with bFGF or EGF (day 4) was inhibited by administration of indomethacin or NS-398, both in the above regimen, and fell to the level obtained without growth factor treatment. These results suggest that COX-2 induced in the sponge granuloma tissues may participate in neovascularization through prostaglandin formation.

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