Bacterial regulation of GI tract cell proliferation

胃肠道细胞增殖的细菌调节

• 批准号: 7226176
• 负责人: SARAH E CHEESEMAN
• 金额: $ 5.04万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226176
• 关键词: Adult; Affect; Animals; Bacteria; Biological Assay; Cell Proliferation; Cell division; Cells; Colorectal Cancer; Coupled; Cultured Cells; Data; Development; Disease; Embryo; Epithelial Cell Proliferation; Epithelial Cells; Epithelium; Equilibrium; Gastrointestinal tract structure; Germ-Free; Growth; Health; Homeostasis; Human; Indigenous; Irritable Bowel Syndrome; Larva; Learning; Mammalian Cell; Modeling; Mus; Neonatal; Numbers; Pattern; Play; Proliferating; Rate; Regulation; Role; Salmonella typhimurium; Siblings; Signal Pathway; Signal Transduction; Testing; Tissues; Transducers; Whole Organism; Zebrafish; beta catenin; gastrointestinal; intestinal epithelium; microbial community; mutant; pathogenic bacteria

DESCRIPTION (provided by applicant): It has long been recognized that pathogenic bacteria can cause various maladies of the gastrointestinal (Gl) tract, but the effects of non-pathogenic, indigenous microbiota on post-natal Gl tract development have been relatively unexplored. Studies reveal the intestinal epithelium of germ free (GF) mice and zebrafish have fewer proliferating cells as compared to conventionally reared siblings. Recently, mammalian cell culture models have suggested that non-pathogenic bacteria can stablize Beta-Catenin, a transducer of Wnt signaling. The balance between proliferating and differentiated cells in the mammalian Gl tract is regulated by Wnt signaling. Collectively, these data motivate a hypothesis that the indigenous microbiota controls the rate of proliferation of the intestinal epithelium through Wnt signaling. This hypothesis will be tested in a whole organism model in which Wnt signaling and the presence and composition of the microbiota can be manipulated. The details of this interaction are relevant to human health, as the activities of the Gl microbiota are implicated in several hyperproliferative diseases of the Gl tract, including irritable bowel syndrome and colorectal cancer.

描述（由申请人提供）：人们早已认识到病原菌可引起胃肠道（GI）的各种疾病，但非病原性本土微生物群对产后胃肠道发育的影响相对尚未被探索。研究表明，与传统饲养的小鼠相比，无菌（GF）小鼠和斑马鱼的肠上皮细胞具有更少的增殖细胞。最近，哺乳动物细胞培养模型表明，非致病性细菌可以稳定 Beta-Catenin（Wnt 信号转导器）。哺乳动物胃肠道中增殖和分化细胞之间的平衡由Wnt信号传导调节。总的来说，这些数据激发了一种假设，即本土微生物群通过 Wnt 信号传导控制肠上皮的增殖速率。这一假设将在整个生物体模型中进行测试，在该模型中可以操纵 Wnt 信号传导以及微生物群的存在和组成。这种相互作用的细节与人类健康相关，因为胃肠道微生物群的活动与胃肠道的几种过度增殖性疾病有关，包括肠易激综合征和结直肠癌。