Altered expression of angiogenic factors in the VEGF-Ets-1 cascades in inflammatory bowel disease

Shiho Konno, Masahiro Iizuka, Michihiro Yukawa, Kenji Sasaki, Akiko Sato, Yasuo Horie, Hiroshi Nanjo, Tsuneo Fukushima, Sumio Watanabe
Journal of Gastroenterology 2004, 39 (10): 931-9

BACKGROUND: The VEGF-Ets-1 cascades play important roles in angiogenesis by converting endothelial cells to an angiogenic phenotype. The aim of this study was to clarify whether the VEGF-Ets-1 cascades are involved in the pathogenesis of inflammatory bowel disease (IBD).

METHODS: Colonic specimens were taken from 42 patients with ulcerative colitis (UC), 37 with Crohn's disease (CD), 8 with non-IBD colitis, and 21 normal controls. (1) Expression of vascular endothelial growth factor (VEGF), VEGF receptors (Flt-1, KDR), and Ets-1 proteins in colonic mucosa was immunohistochemically examined using specific antibodies. (2) Expression of Ets-1 protein or VEGF, Flt-1, KDR, and Ets-1 mRNA in colonic mucosa was measured by Western blot or RT-PCR.

RESULTS: (1) The number of VEGF-containing cells was significantly increased in active UC ( P <0.05). The numbers of positive blood vessels (mean +/- SE /mm2) to Flt-1, KDR, and Ets-1 antibodies were significantly increased in active UC (Flt-1: 4.0 +/- 0.84; KDR: 2.4 +/- 0.37; Ets-1: 5.5 +/- 0.77) compared to active CD (Flt-1: 0.6 +/- 0.30; KDR: 0.77 +/- 0.28; Ets-1: 2.0 +/- 0.56) ( P <0.01), non-IBD colitis (Flt-1: 1.0 +/- 0.45; KDR: 1.83 +/- 0.54; Ets-1: 3.0 +/- 1.0), and controls (Flt-1: 0.88 +/- 0.40; KDR: 0.60 +/- 0.22; Ets-1: 1.67 +/- 0.47) ( P <0.01). The numbers of positive cells to these antibodies were also increased in active UC. (2) Expression of Ets-1 protein and Flt-1, KDR, and Ets-1 mRNA was increased in active UC.

CONCLUSIONS: Angiogenic factors in the VEGF-Ets-1 cascades were upregulated in UC, but they were relatively downregulated in CD. These alterations might be involved in the pathogenesis of both diseases.

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