三叶草肽Ⅲ（TFF3）调节肠上皮细胞核转录因子NF-κB及其新的负反馈调节子扭蛋白Twist的机制：TFF3与肿瘤坏死因

发布时间：2018-05-09 09:08

本文选题：肠上皮细胞 + 三叶草因子　；参考：《中国医科大学》2006年博士论文

【摘要】：目的核转录因子κB(NF-κB)是调解炎症,免疫等生物过程的中心性核转录因子。它的作用取决于细胞及刺激类型。研究显示细胞外刺激激活的NF-κB,主要受其上游的IKK激酶调控后的IκB降解表达进行调节。激活的NF-κB复合物转入细胞核,与靶基因启动子结合行使其转录调节功能。最近,增长的事实显示:哺乳类细胞中存在NF-κB激活的负性调节通路网络。例如:NF-κB的激活不仅导致炎症,存活等相关基因合成上调,也进行NF-κB依赖的NF-κB负性调节子合成及再合成。NF-κB的负性调节通路能够保证细胞内信号的瞬时产生以防止未被调控的NF-κB的激活。在体内,通过终止,阻断前炎症因子诱导的NF-κB活性以限制炎症性损伤是至关重要的。扭蛋白Twist是以螺旋-环式-螺旋为基本结构的转录因子。最近,Sosic等人证明:1) 扭蛋白Twist与转录因子NF-κB相互作用;2) 在体内,扭蛋白Twist是下调核转录因子NF-κB活性的基本调节子;3) 转录因子NF-κB调节扭蛋白Twist表达。所以,扭蛋白是转录因子NF-κB重要的调节蛋白。它在参与NF-κB通路的负性调节及减缓炎症的应答中起到重要的作用。一组研究也显示扭蛋白存在于哺乳类上皮细胞系中,这提示扭蛋白可能参与上皮组织的生理及病理生理调解过程。三叶草肽(TFF)为细胞外肽家族。最初,它们被发现在胃肠道。
[Abstract]:Purpose NF-魏 B is a central nuclear transcription factor that mediates inflammation, immunity and other biological processes. Its effect depends on the cell and the type of stimulus. Studies have shown that extracellular stimulation-activated NF- 魏 B is mainly regulated by I 魏 B degradation and expression regulated by upstream IKK kinase. The activated NF- 魏 B complex was transferred into the nucleus and combined with the target gene promoter to perform its transcriptional regulation. Recently, the growth of mammalian cells shows that NF- 魏 B activated negative regulatory pathway networks exist in mammalian cells. For example, the activation of: NF- 魏 B not only leads to up-regulation of gene synthesis, such as inflammation, survival, etc. The negative regulatory pathway of NF- 魏 B dependent NF- 魏 B and its resynthesis can guarantee the transient production of intracellular signal and prevent the activation of unregulated NF- 魏 B. In vivo, it is important to block the activity of NF- 魏 B induced by preinflammatory factor in vivo. Torsion protein Twist is a transcription factor with helix-loop-helix as its basic structure. Recently, Sosic et al have demonstrated that writhing protein Twist interacts with transcription factor NF- 魏 B in vivo. In vivo, torsion protein Twist is the basic regulator of down-regulation of the activity of nuclear transcription factor NF- 魏 B. The transcription factor NF- 魏 B regulates the expression of twisted protein Twist. Therefore, twisted protein is an important regulatory protein of transcription factor NF- 魏 B. It plays an important role in the negative regulation of NF- 魏 B pathway and slowing the inflammatory response. A group of studies have also shown that twisted protein is present in mammalian epithelial cell lines, suggesting that it may be involved in the physiological and pathophysiological mediation of epithelial tissue. TFF is a family of extracellular peptides. Initially, they were found in the gastrointestinal tract.
【学位授予单位】：中国医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R341

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