Bacterial regulation of GI tract cell proliferation

胃肠道细胞增殖的细菌调节

• 批准号: 7127731
• 负责人: SARAH E CHEESEMAN
• 金额: $ 4.88万
• 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/7127731
• 关键词: Salmonella typhimurium; biological signal transduction; cadherins; cell cycle; cell proliferation; enteric bacteria; gastrointestinal disorder; gastrointestinal epithelium; gene mutation; germ free condition; green fluorescent proteins; histogenesis; host organism interaction; intestines; larva; postdoctoral investigator; tissue /cell culture; zebrafish

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(申请人提供)：长期以来，人们已经认识到病原菌可以引起胃肠道(Gl)的各种疾病，但非致病性的本土微生物群对出生后Gl道发育的影响还相对未被探索。研究表明，与传统饲养的兄弟姐妹相比，无菌(GF)小鼠和斑马鱼的肠道上皮细胞增殖细胞较少。最近，哺乳动物细胞培养模型表明，非致病细菌可以稳定Wnt信号的转导因子Beta-catenin。哺乳动物Gl区增殖细胞和分化细胞之间的平衡受Wnt信号的调节。总而言之，这些数据支持一种假设，即本土微生物区系通过Wnt信号控制肠道上皮的增殖速度。这一假设将在整个生物体模型中得到验证，在该模型中，Wnt信号以及微生物区系的存在和组成可以被操纵。这种相互作用的细节与人类健康有关，因为Gl微生物区系的活动与Gl肠道的几种过度增殖疾病有关，包括肠易激综合征和结直肠癌。