Study on the molecular basis of the response of the digestive tract evoked by nutrients/functional food factors

营养素/功能性食品因子引起消化道反应的分子基础研究

• 批准号: 15590213
• 负责人: GODA Toshinao
• 金额: $ 2.3万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590213/
• 关键词: intestine; nuclear receptor; transcription; fatty acid; retinoic acid; phosphorylation; development; proteomics; フルクトース; 甲状腺ホルモン; 脱リン酸化

1. Transcription factors involved in the expression of digestion/absorption-related genes during development: In the perinatal period, the expression of cellular retinol-binding protein, type II (CRBPII) was abruptly elevated in rat small intestine. This was accompanied by a coordinated and marked expression of RXR α and HNF-4 in the nuclei of villus cells. The gene expression of RALDH1 and RALDH2 involved in the generation of retinoic acid was elevated in the liver and small intestine just before birth. The organ culture of the small intestine obtained just before birth showed an induction of CRBPII gene in the presence of RXR α ligand.2. The expression of transcription factors related to digestion and absorption in the small intestine and the modulation induced by phosphorylation.: Rats fed a high-fat diet showed a greater expression of CRBPII from the base to the tip of the villi. In these animals, the gene expression of PPAR α and HNF-4 were coordinately elevated, while that of PPAR δ was reduced. The proteomics analysis of PPAR δ target genes using C2BBe1 revealed that HMG-CoA synthase and glutathione S transferase were induced by PPAR δ ligand. The forskolin-induced phosphorylation of HNF-4 caused the reduction of the binding activity of HNF-4 to the DR-1 element on the CRBPII gene promoter. These results suggest that the basic expression of CRBPII is maintained by HNF-4, and its level is modulated by RXR α ligand.3. Mechanism involved in the diurnal variation of the expression of digestion/absorption-related genes: The expression of CRBPII in rat jejunum showed a diurnal variation at a transcriptional level, which depended on the dietary fat content, and lost in rats fed a fat-free diet. These results suggest that dietary fatty acids may play a role in the diet-induced diurnal variation of CRBPII gene expression.

1. 发育过程中参与消化/吸收相关基因表达的转录因子：在围产期，大鼠小肠细胞视黄醇结合蛋白II型（CRBPII）的表达突然升高。这与绒毛细胞细胞核中RXR α和HNF-4的协调和显著表达相伴随。胎儿出生前肝脏和小肠中参与维甲酸生成的RALDH1和RALDH2基因表达升高。在出生前获得的小肠器官培养中，RXR α配体的存在诱导了CRBPII基因的表达。小肠消化吸收相关转录因子的表达及磷酸化诱导的调控。：高脂肪饮食的大鼠从绒毛基部到绒毛尖端的CRBPII表达更高。在这些动物中，PPAR α和HNF-4的基因表达协调升高，而PPAR δ的基因表达降低。利用C2BBe1对PPAR δ靶基因进行蛋白质组学分析，发现PPAR δ配体诱导了HMG-CoA合成酶和谷胱甘肽S转移酶。福斯克林诱导的HNF-4磷酸化导致HNF-4与CRBPII基因启动子上DR-1元件的结合活性降低。这些结果表明，HNF-4维持了CRBPII的基本表达，其水平受RXR α配体的调节。消化/吸收相关基因表达日变化的机制：CRBPII在大鼠空肠中的表达在转录水平上呈现日变化，这取决于饮食中的脂肪含量，在喂食无脂肪饮食的大鼠中表达消失。这些结果表明，膳食脂肪酸可能在饮食诱导的CRBPII基因表达的日变化中发挥作用。

项目成果

Developmental changes of the expression of the genes regulated by retinoic acid in the small intestine of rats.

大鼠小肠视黄酸调控基因表达的发育变化。

• 发表时间: 2005
• 期刊: Life Science (印刷中)
• 作者: Y.Ogura;K.Suruga;S.Takase;T.Goda
• 通讯作者: T.Goda

合田敏尚: "健康・栄養食品アドバイザリースタッフテキストブック"第一出版. 336 (2003)

合田敏久：《健康与营养食品咨询人员教科书》第一出版336（2003）。

Diet-related diurnal variation of cellular retinol-binding protein, type II gene expression in rat jejunum.

大鼠空肠中细胞视黄醇结合蛋白 II 型基因表达的饮食相关昼夜变化。

• 发表时间: 2005
• 期刊: British Journal of Nutrition (印刷中)
• 作者: K.Suruga;M.Kitagawa;H.Yasutake;S.Takase;T.Goda
• 通讯作者: T.Goda

ILSIジャパン

日本ILSI

• 发表时间: 2004
• 作者: Fukushima;A.;Gouda;T.et al.;合田 敏尚;合田敏尚;合田敏尚
• 通讯作者: 合田敏尚

ラット小腸および肝臓におけるβカロテン開裂酵素遺伝子の発現変動とプロモーター領域の解析

大鼠小肠和肝脏β-胡萝卜素裂解酶基因表达变化及启动子区分析

• 发表时间: 2005
• 期刊: 消化と吸収 27・2(印刷中)
• 作者: Suruga;K.;Kitagawa;M.;Yasutake;H.;Takase;S.;Goda;T.;合田 敏尚
• 通讯作者: 合田 敏尚