Journal of Gastroenterology

, Volume 38, Issue 3, pp 229-237

First online:

Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease

  • Shinsuke SaitoAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Nelson H. TsunoAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Eiji SunamiAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Nobukazu HoriAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Joji KitayamaAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Shinsuke KazamaAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Yurai OkajiAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Kazushige KawaiAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • , Takamitsu KanazawaAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
    • , Toshiaki WatanabeAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
    • , Yoichi ShibataAffiliated with Department of Transfusion Medicine, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
    • , Hirokazu NagawaAffiliated with Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Tokyo, Japan

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Background:

Platelet-derived endothelial cell growth factor (PD-ECGF) is reported to be highly expressed in tumors and inflammatory tissues, but its expression and role in inflammatory bowel disease (IBD) are still unclear. In this study we examined the location and tissue density of cells immunoreactive for PD-ECGF in the colonic mucosa of IBD. Methods: Paraffin-embedded sections of colonic tissue from patients with ulcerative colitis (UC) or Crohn's disease (CD) were immunostained for PD-ECGF. As controls, noninflamed mucosa of IBD, as well as normal colonic mucosa from patients with colorectal cancer, were used. Also, cancer tissues were evaluated. In addition, changes in the expression of PD-ECGF in human umbilical vein endothelial cells (HUVEC) after treatment with inflammatory cytokines and angiogenic factors, as well as after coculture with colon cancer cell lines, were evaluated by flow cytometry. Results: In normal colonic mucosa and noninflamed mucosa of IBD, PD-ECGF expression was negligible. In inflamed colonic mucosa, strong expression was observed, predominantly in macrophages and fibroblasts. Vascular endothelial cells of the inflamed colonic mucosa, but not of normal colonic mucosa or of neoplastic tissues, stained for PD-ECGF, and the microvessel density was significantly increased in the severely inflamed mucosa. Flow cytometry demonstrated that PD-ECGF was constitutively expressed in HUVEC. Inflammatory cytokines and vascular endothelial growth factor (VEGF) increased its expression, whereas basic fibroblast growth factor (bFGF) decreased it. Coculture with colon cancer cell lines in direct contact, but not in those without contact, also resulted in an important decrease in the expression of PD-ECGF in HUVEC. Conclusions: Autocrine production of PD-ECGF by endothelial cells may be a mechanism of inflammatory angiogenesis, but not tumor angiogenesis, and may be particularly important for the maintenance of damaged vasculature in IBD.

Key words: platelet-derived endothelial cell growth factor ulcerative colitis Crohn's disease endothelial cell angiogenesis