Identification of Colon-specifi abnormal gene expression in alcerative colitis.

阿尔茨海默病结肠炎中结肠特异性异常基因表达的鉴定。

• 批准号: 10470252
• 负责人: FUKUSHIMA Kouhei
• 金额: $ 8.26万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470252/
• 关键词: epithelial cell; inflammatory bowel disease; Ulcerative colitis; germ-free; クーロン病; 炎症性腸疾患

A total of 300 displays with different sets of primers were carried out. Bands were selected after at least 2 displays using the same combination of primers. Some genes such as reg IIIβ, IIIγ and carbonic anhydrase I were selected in multiple displays with different sets of primers. We successfully cloned 118 bands. Sixty-eight clones out of 118 (58%) were used as probes in northern blotting to confirm differential gene expression among GF, bacteria-reconstituted and specific pathogen-free (SPF) mice, or between the small intestine and the colon. To evaluate the significance and specificity of gene modulation in the bacterial reconstitution model, we established dextran sulfate sodium (DSS) induced-colitis as an inflammatory control. RNAs from DSS-colitis were also used in some experiments.We clearly demonstrate in the following that our bacterial reconstitution model and epithelial gene screening truly detects human genes associated with IBD, suggesting that some genes listed in table 1 and 2 must be involved in human IBD.We concentrated two molecules. We demonstrated epithelial induction of serum amyloid A(SAA) in IBD and modulatory activity of SAA in LPS-associated inflammation. We additionally showed epithelial induction of Regenerating gene III and HIP/PAP in experimental and human inflammatory bowel disease in association with Paneth cell metaplasia.In summary, we successfully identified genes modulated in human IBD by analyzing bacteria reconstitution model and investigating human homologues

总共进行了300次使用不同套引物的展示。在使用相同的引物组合进行至少2次展示后选择条带。用不同的引物在多重显示中选择了一些基因，如reg IIIβ、IIIγ和碳酸氢酶I。我们成功克隆了118条谱带。使用118个克隆中的68个(58%)作为探针进行Northern杂交，以确认GF、细菌重组和无特定病原体(SPF)小鼠之间，或者在小肠和结肠之间的差异基因表达。为了评价基因调控在细菌重建模型中的意义和特异性，我们建立了葡聚糖硫酸钠(DSS)诱导的结肠炎作为炎症对照。DSS-结肠炎的RNA也被用于一些实验。我们在以下方面清楚地证明了我们的细菌重建模型和上皮基因筛选确实检测到了与IBD相关的人类基因，这表明表1和表2中列出的一些基因肯定参与了人类IBD。我们证明了在IBD中上皮细胞诱导血清淀粉样蛋白A(SAA)，并在内毒素相关的炎症中调节SAA的活性。此外，我们还展示了实验性和人类炎症性肠病中再生基因III和HIP/PAP的上皮诱导与Paneth细胞化生相关。综上所述，我们通过分析细菌重建模型和研究人类同源物，成功地识别了在人类IBD中调控的基因

项目成果

Urocortine and corticotropin-rellasing factor-receptor expression in the human colonic mucosa.

尿皮质素和促肾上腺皮质激素释放因子受体在人结肠粘膜中的表达。

• 发表时间: 2000
• 期刊: Peptide 21
• 作者: Y.Muramatsu;K.Fukushima et al.
• 通讯作者: K.Fukushima et al.

K.Takahashi, K.Fukushima et al.: "Identification of sells responding to Orsoactive Infegtinal Peptide in Human Colonic Mucosa"Scand. J. Gastroenterol. 35. 737-741 (2000)

K.Takahashi、K.Fukushima 等人：“对人类结肠粘膜中 Orsoactive Infegtinal Peptide 的响应的识别”Scand。

福島 浩平: "Endotoxin contamination in isolation of lemina propria mono nuclear cells"Tohoku J. Experimental Meducine. 187. 37-42 (1999)

Kohei Fukushima：“分离固有菌单核细胞时的内毒素污染”Tohoku J. Experimental Meducine 187. 37-42 (1999)。

Y.muramatsu, K.Fukushima et al.: "Urocorfin and corficonfropin-releasing factor receptor expression in the human colonic mucosa"Pentides. 21. 1799-1809 (2000)

Y.muramatsu、K.Fukushima 等人：“Urocorfin 和 corficonfropin 释放因子受体在人结肠粘膜中的表达”Pentides。

福島浩平: "Lipopoly Saccharide and proinflammatory cytokines induced energy production in intestinal and Colonic enithelial cell lines" Scandinavian journal of Gast roenterology. (in press).

Kohei Fukushima：“脂多糖和促炎细胞因子诱导肠道和结肠上皮细胞系的能量产生”斯堪的纳维亚胃肠病学杂志（正在出版）。