Konno Shiho, Iizuka Masahiro, Yukawa Michihiro, Sasaki Kenji, Sato Akiko, Horie Yasuo, Nanjo Hiroshi, Fukushima Tsuneo, Watanabe Sumio
Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, 010-8543, Akita, Japan.
J Gastroenterol. 2004 Oct;39(10):931-9. doi: 10.1007/s00535-004-1423-9.
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).
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.
(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.
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.
血管内皮生长因子（VEGF）-Ets-1级联反应通过将内皮细胞转变为血管生成表型在血管生成中发挥重要作用。本研究旨在阐明VEGF-Ets-1级联反应是否参与炎症性肠病（IBD）的发病机制。
取自42例溃疡性结肠炎（UC）患者、37例克罗恩病（CD）患者、8例非IBD结肠炎患者以及21例正常对照者的结肠标本。（1）使用特异性抗体通过免疫组织化学方法检测结肠黏膜中血管内皮生长因子（VEGF）、VEGF受体（Flt-1、KDR）和Ets-1蛋白的表达。（2）通过蛋白质印迹法或逆转录聚合酶链反应（RT-PCR）检测结肠黏膜中Ets-1蛋白或VEGF、Flt-1、KDR和Ets-1 mRNA的表达。
（1）活动期UC中含VEGF的细胞数量显著增加（P<0.05）。与活动期CD（Flt-1：0.6±0.30；KDR：0.77±0.28；Ets-1：2.0±0.56）（P<0.01）、非IBD结肠炎（Flt-1：1.0±0.45；KDR：1.83±0.54；Ets-1：3.0±1.0）及对照组（Flt-1：0.88±0.40；KDR：0.60±0.22；Ets-1：1.67±0.47）（P<0.01）相比，活动期UC中对Flt-1、KDR和Ets-1抗体呈阳性的血管数量（平均值±标准误/mm²）显著增加。对这些抗体呈阳性的细胞数量在活动期UC中也增加。（2）活动期UC中Ets-1蛋白以及Flt-1、KDR和Ets-1 mRNA的表达增加。
VEGF-Ets-1级联反应中的血管生成因子在UC中上调，但在CD中相对下调。这些改变可能参与了两种疾病的发病机制。
