VEGF, Basic-FGF, and TGF-β in Crohn's Disease and Ulcerative Colitis : A Novel Mechanism of Chronic Intestinal Inflammation

克罗恩病和溃疡性结肠炎中的 VEGF、Basic-FGF 和 TGF-β：慢性肠道炎症的新机制

• 批准号: 13671360
• 负责人: TSUNODA Tsukasa
• 金额: $ 1.86万
• 依托单位: KAWASAKI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671360/
• 关键词: ulcerative colitis; Crohn's disease; endothelin-1; vascular endothelial growth factor; basic fibroblast growth factor; transforming growth factor-β; vasculitis; intestinal ischemia

Objective : Inflammatory bowel disease(IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation ; ulcerative colitis(UC) and Crohn's disease(CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assessed serum concentration levels of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b-FGF), and plasma level of endothelin-1(ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-β 1,2,3(TGF-β_<1,2,3>) in tissue by immunostaining.Methods : Blood samples were obtained from 11 patients with UC,11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemicar study.Results : The concentra … More tion levels(in picograms per milliliter) were as follows : for ET-1,UC:127±47.0,CD:167.3±35.1,and controls(asthma:38.5±23.8 p<0.01;diverticulitis:40.5±25.6, p<0.01), for b-FGF,UC:9.2±1.9,CD:9.1±1.5,and controls(asthma:5.0±0,p<0.01;diverticulitis:5.0±0.p<0.01), for VEGF,UC:659.8±181.0,CD:740.0±182.3,and controls(asthma:193.7±58.7,p<0.01;diverticulitis:199.6±59.7,p<0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF, and the plasma level of ET-1;that is, elevated VEGF,b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-β_2 and TGF-β_3 were found in inflammatory cells of active IBD, but no change was observed aroud the vessels in the controls.Conclusion : It is suggested that the reciprocal reaction of these cytokines may contribute to angibgenesis in IBD by inducing intestinal ischemia through vasoconstriction. Less

目的：炎症性肠病（IBD），其确切病因仍然未知，由两种形式的慢性肠道炎症组成：溃疡性结肠炎（UC）和克罗恩病（CD）。最近的证据越来越多地表明，IBD是由粘膜细胞因子的不适当产生所表现的免疫调节功能障碍的结果。其发病机制也涉及异常的微循环系统。为了阐明IBD缺血性变化的机制，我们评估了血清血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（b-FGF）的浓度水平，以及血浆内皮素-1（ET-1）的水平。方法：采用免疫组化法检测11例UC患者、11例CD患者和10例正常对照者的外周血中VEGF、b-FGF和转化生长因子-β 1，2，3（TGF-β 1，2，3）的表达。石蜡包埋的样品用于药物化学研究。 ...更多信息 离子水平ET-1组UC为127± 47.0，CD为167.3± 35.1，对照组为127± 47.0，（哮喘：38.5±23.8，p<0.01;憩室炎：40.5±25.6，p<0.01），对于b-FGF，UC：9.2± 1.9，CD：9.1± 1.5，对照组（哮喘：5.0±0，p<0.01;憩室炎：5.0±0.p<0.01），对于VEGF，UC：659.8± 181.0，CD：740.0± 182.3，对照组（哮喘组：193.7± 58.7，p <0.01;憩室炎组：199.6± 59.7，p <0.01）。活动期IBD患者血清VEGF和b-FGF水平明显高于对照组。血清VEGF和b-FGF水平与血浆ET-1水平之间存在显著正相关性;即VEGF、b-FGF和ET-1水平升高彼此相关性良好。免疫组化研究显示，增加微静脉粘膜下层和固有层。结果：IBD活动期血管内皮细胞VEGF、b-FGF表达增强，炎性细胞TGF-β_2、TGF-β_3表达增强，而对照组血管周围无明显变化。结论：IBD时血管内皮细胞VEGF、b-FGF表达增强，炎性细胞TGF-β_2、TGF-β_3表达增强。少

项目成果

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Atsushi Urakami、Tsukasa Tsunoda 等：“胰腺假性囊肿进入结肠和十二指肠的自发性瘘管”Gastrointest Endosc. 949-951 (2002)。

岩本末治, 角田 司: "消化器ナビゲーター-胆道の手術-"メディカルレビュー社. 4 (2002)

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