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

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，大鼠小肠中细胞视黄醇结合蛋白II型（CRBPII）的表达突然升高。RXR α和HNF-4在绒毛细胞核中的表达明显增强。RALDH 1和RALDH 2参与维甲酸的产生的基因表达在出生前在肝脏和小肠中升高。出生前获得的小肠器官培养显示，在RXR α配体存在下，CRBPII基因被诱导.与小肠消化吸收相关的转录因子的表达及磷酸化诱导的调节。喂食高脂饮食的大鼠从绒毛的基部到尖端显示出更大的CRBPII表达。在这些动物中，PPAR α和HNF-4的基因表达协同升高，而PPAR δ的基因表达降低。利用C2BBe 1对PPAR δ靶基因进行蛋白质组学分析，发现HMG-CoA合成酶和谷胱甘肽S转移酶受PPAR δ配体的诱导。毛喉素诱导的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，CRBPII的基本表达由HNF-4维持，其水平受RXR α配体调节.消化/吸收相关基因表达的日变化机制：大鼠空肠CRBPII的表达在转录水平上呈现日变化，依赖于膳食脂肪含量，在无脂饮食大鼠中表达丢失。这些结果表明，膳食脂肪酸可能在饮食诱导的CRBPII基因表达的昼夜变化中发挥作用。

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.