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Probiotic Bacteria and the Gastrointestinal Barrier: miRNAs, Signaling Pathways and Molecular Repair Mechanisms

益生菌和胃肠道屏障：miRNA、信号通路和分子修复机制

基本信息

批准号：
213208174
负责人：
Professor Dr. Marcus Alexander Schmidt
金额：
--
依托单位：
Institut für Infektiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/213208174?language=en
关键词：
Probiotic Bacteria Gastrointestinal Barrier miRNAs

项目摘要

The intestinal ecosystem is characterized by a dynamic and balanced interaction between the resident microflora, the gastrointestinal barrier (GIB) and the (mucosal) immune system. In chronic inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn's disease, this balance is disturbed. Probiotic bacteria (e.g. E. coli Nissle 1917 (EcN) or lactobacilli) stabilize and/or regenerate the GIB by modulating intercellular junctions. However, the mechanisms underlying these effects are currently only poorly understood. This project aims at the elucidation of signaling pathways induced by Gram-negative and Gram-positive probiotics, the analysis of the relevant cellular targets in intestinal epithelial cells and in particular at cellular factors such as miRNAs involved in the regulation of barrier-relevant target structures. For probiotic bacteria, the responsible factors ('trigger factors') for the induction of signaling pathways are to be identified and characterized. Identification of microRNAs involved in the regulation of the epithelial barrier might potentially also provide new therapeutic applications. Therefore, as another aspect of this project the possible application of 'pre-miRNA' coupled to 'nanobeads', or alternatively ’ß1,3-D-glucan-encapsulated miRNA particles (GeRPs = ’yeast ghosts ’)’ or ’exosomes’ will be tested for potential application in a mouse model of IBD. For this, cell-penetrating peptides will also be employed for intracellular delivery.

肠道生态系统的特征在于常驻微生物菌群、胃肠道屏障（GIB）和（粘膜）免疫系统之间的动态和平衡的相互作用。在慢性炎症性肠病（IBD），如溃疡性结肠炎和克罗恩病，这种平衡被打乱。益生菌（如E. coli Nissle 1917（EcN）或乳酸杆菌）通过调节细胞间连接稳定和/或再生GIB。然而，这些影响的机制目前还知之甚少。该项目旨在阐明革兰氏阴性和革兰氏阳性益生菌诱导的信号通路，分析肠上皮细胞中的相关细胞靶点，特别是参与屏障相关靶结构调节的细胞因子，如miRNA。对于益生菌，将鉴定和表征诱导信号传导途径的负责因子（“触发因子”）。鉴定参与上皮屏障调节的microRNA也可能提供新的治疗应用。因此，作为该项目的另一方面，将测试偶联到“纳米珠”或替代地“β 1，3-D-葡聚糖包封的miRNA颗粒（GeRP =”酵母菌影“）”或“外来体”的“前体miRNA”在IBD小鼠模型中的潜在应用。为此，细胞穿透肽也将用于细胞内递送。