Enhanced Expressions of Endothelin-Converting Enzyme and Endothelin Receptors in Human Colonic Tissues of Crohn's Disease

DOI 28 References
  • Suekane Takehisa
    Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Ikura Yoshihiro
    Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Arimoto Junko
    Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Nakagawa Masashi
    Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Kitabayashi Chizuko
    Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Naruko Takahiko
    Department of Cardiology, Osaka City General Hospital, Osaka 534-0021, Japan
  • Watanabe Toshio
    Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Fujiwara Yasuhiro
    Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Oshitani Nobuhide
    Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Maeda Kiyoshi
    Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Tanzawa Kazuhiko
    Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, Japan
  • Hirakawa Kosei
    Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Arakawa Tetsuo
    Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
  • Ueda Makiko
    Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan

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Abstract

Endothelin-1, a powerful vasoconstrictor, forms the endothelin system together with endothelin-converting enzyme and endothelin type A and type B receptors. These endothelin system components are considered to participate in inflammatory and wound healing responses. Previous reports have suggested a role for the endothelin-1 in the pathology of Crohn’s disease. In the present study, we immunohistochemically investigated the expressions of the endothelin system components in affected human intestinal tissues of Crohn’s disease. Eighteen surgical specimens of colonic tissue obtained from patients with Crohn’s disease and 12 normal colonic tissues as controls were examined. Frozen tissue sections cut from the samples were subjected to the immunohistochemical single and double staining. The endothelin system components were expressed mainly in the muscular layers and blood vessels. In diseased colonic tissues, inflammatory infiltration and fibrotic tissue reactions with marked smooth muscle cell proliferation were frequently seen, and were closely associated with increased expressions of the endothelin system components. These results strongly suggest that endothelin-converting enzyme and endothelin type A and type B receptors collectively play a role in the inflammatory and fibrogenic processes of Crohn’s disease. Especially, submucosal smooth muscle proliferation, a histological hallmark of strictures, may be attributable to the upregulated endothelin system.<br>

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